7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
Ligand (β-blocker) induce EGFR internalazation |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
Ligand (β-blocker) induce EGFR transactivation and ERK activation |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
Ligand (β-blocker) significantly increased ERK activation in mouse heart |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
β1ARs without C-tail phosphorylation sites prevent EGFR transactivation |
Knock in - mutant receptor with impared signalling |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
siRNS targeting β-arr1, β-arr2 or both significantly blocked ERK activation |
Gene silencing (siRNA) of sig. prot. |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7158
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
alprenolol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
Ligand (β-blocker) induce EGFR internalazation |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7158
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
alprenolol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
Ligand (β-blocker) induce EGFR transactivation and ERK1/2 activation |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7158
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
alprenolol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
Ligand (β-blocker) significantly increased ERK activation in mouse heart |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7158
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
alprenolol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
β1ARs without C-tail phosphorylation sites prevent EGFR transactivation |
Knock in - mutant receptor with impared signalling |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
7158
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
alprenolol
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects |
siRNS targeting β-arr1, β-arr2 or both significantly blocked ERK activation |
Gene silencing (siRNA) of sig. prot. |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA |
105:14555-60 |
8236
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
dobutamine
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
β1ARs without C-tail phosphorylation sites prevent EGFR transactivation and internalization plus leads to only minimal ERK activation |
Knock in - mutant receptor with impared signalling |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8236
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
dobutamine
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
Robust membrane translocation of GFP-β-arr |
Tagged sig. prot |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8236
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
dobutamine
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
siRNS targeting β-arr1, β-arr2 or both significantly blocked EGFR transactivation and associated ERK activation |
Gene silencing (siRNA) of sig. prot. |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8236
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
dobutamine
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
siRNA targeting of β-arrestin1/2 blocked EGFR internalization |
Gene silencing (siRNA) of sig. prot. |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
siRNA targeting of β-arrestin1/2 blocked EGFR internalization |
Gene silencing (siRNA) of sig. prot. |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8236
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
dobutamine
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
ERK activation was completely blocked in the β-arrestin2–knockout mice |
Knock out of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
Cardiac contractility was significantly enhanced indicating a state of diminished βAR desensitization |
Knock in - mutant receptor with impared signalling |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
βAR density reduced in WT after chronic agonist treatment but not in mutant. |
Knock in - mutant receptor with impared signalling |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
Significant deterioration in cardiac function with marked LV dilatation and reduced fractional shortening |
Knock in - mutant receptor with impared signalling |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. |
Increased interstitial fibrosis and apoptotic nuclei |
Knock in - mutant receptor with impared signalling |
Animals |
Histological examination |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
7747
|
A |
Apelin receptors |
APJ |
apelin |
Human |
CMF-019
|
gi/o-family |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Ligand showed bias towards G-protein signalling whereas β-arrestin mediated receptor desensitisation and internalisation was less potent |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Read C, Fitzpatrick CM, Yang P, Kuc RE, Maguire JJ, Glen RC, Foster RE, Davenport AP |
116:63-72 |
7747
|
A |
Apelin receptors |
APJ |
apelin |
Rat |
CMF-019
|
gi/o-family |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Ligand showed similar cardiac contractility compared to full agonist |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Read C, Fitzpatrick CM, Yang P, Kuc RE, Maguire JJ, Glen RC, Foster RE, Davenport AP |
116:63-72 |
7747
|
A |
Apelin receptors |
APJ |
apelin |
Rat |
CMF-019
|
gi/o-family |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Ligand didn't show any vasodialtory response compared to full agonist |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Read C, Fitzpatrick CM, Yang P, Kuc RE, Maguire JJ, Glen RC, Foster RE, Davenport AP |
116:63-72 |
9183
|
A |
Cannabinoid receptors |
CNR2 |
CB2 |
Mouse |
LY2828360
|
gi/o-family |
|
Nervous system disease |
Analgesia |
Bias towards G-protein signalling attenuated chemotherapy-induced neuropathic pain without developing tolerance |
Ligand showed bias towards G-protein signalling whereas β-arrestin mediated receptor desensitisation and internalisation was absent |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG |
93:49-62 |
9183
|
A |
Cannabinoid receptors |
CNR2 |
CB2 |
Mouse |
LY2828360
|
gi/o-family |
|
Nervous system disease |
Analgesia |
Bias towards G-protein signalling attenuated chemotherapy-induced neuropathic pain without developing tolerance |
Bias towards G-protein signalling confirmed by pertussis toxin (PTX) treatment. Biased ligand showed delayed G-protein activation compared to full agonist |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG |
93:49-62 |
9183
|
A |
Cannabinoid receptors |
CNR2 |
CB2 |
Mouse |
LY2828360
|
gi/o-family |
|
Nervous system disease |
Analgesia |
Bias towards G-protein signalling attenuated chemotherapy-induced neuropathic pain without developing tolerance |
Treatment with biased ligand resulted in G-protein mediated ERK activation only whereas ERK activation by β-arrestin was absent |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG |
93:49-62 |
9183
|
A |
Cannabinoid receptors |
CNR2 |
CB2 |
Mouse |
LY2828360
|
gi/o-family |
|
Nervous system disease |
Analgesia |
Bias towards G-protein signalling attenuated chemotherapy-induced neuropathic pain without developing tolerance |
Biased ligand reversed the paclitaxel-induced allodynic effects |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG |
93:49-62 |
9183
|
A |
Cannabinoid receptors |
CNR2 |
CB2 |
Mouse |
LY2828360
|
gi/o-family |
|
Nervous system disease |
Analgesia |
Bias towards G-protein signalling attenuated chemotherapy-induced neuropathic pain without developing tolerance |
Biased ligand blocked the development of tolerance to anti-allodynic effects of morphine |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG |
93:49-62 |
9183
|
A |
Cannabinoid receptors |
CNR2 |
CB2 |
Mouse |
LY2828360
|
gi/o-family |
|
Nervous system disease |
Analgesia |
Bias towards G-protein signalling attenuated chemotherapy-induced neuropathic pain without developing tolerance |
Biased ligand showed anti-allodynic effects in morphine tolerant mice |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG |
93:49-62 |
9183
|
A |
Cannabinoid receptors |
CNR2 |
CB2 |
Mouse |
LY2828360
|
gi/o-family |
|
Nervous system disease |
Analgesia |
Bias towards G-protein signalling attenuated chemotherapy-induced neuropathic pain without developing tolerance |
Biased ligand reduced withdrawal symptoms post naloxone challenge |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG |
93:49-62 |
178695
|
A |
Dopamine receptors |
DRD1 |
D1 |
Rat |
CHEMBL4469983
|
gs-family |
|
Psychiatric disorder |
Neuroprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby enhancing the dopaminergic signalling pathway |
Impaired β-arrestin recruitment lead to decrease in desensitisation by the biased ligand |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Gray DL, Allen JA, Mente S, O'Connor RE, DeMarco GJ, Efremov I, Tierney P, Volfson D, Davoren J, Guilmette E, Salafia M, Kozak R, Ehlers MD |
9:674 |
178695
|
A |
Dopamine receptors |
DRD1 |
D1 |
Human |
CHEMBL4469983
|
gs-family |
|
Psychiatric disorder |
Neuroprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby enhancing the dopaminergic signalling pathway |
Biased ligand failed to re-locate β-arrestin on the plasma membrane post agonist stimulation |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Gray DL, Allen JA, Mente S, O'Connor RE, DeMarco GJ, Efremov I, Tierney P, Volfson D, Davoren J, Guilmette E, Salafia M, Kozak R, Ehlers MD |
9:674 |
178695
|
A |
Dopamine receptors |
DRD1 |
D1 |
Rat |
CHEMBL4469983
|
gs-family |
|
Psychiatric disorder |
Neuroprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby enhancing the dopaminergic signalling pathway |
Biased ligand enhanced rotational behaviour in rodents which is a functional correlate of reduced desensitisation and enhanced dopaminergic signalling |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Gray DL, Allen JA, Mente S, O'Connor RE, DeMarco GJ, Efremov I, Tierney P, Volfson D, Davoren J, Guilmette E, Salafia M, Kozak R, Ehlers MD |
9:674 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Biased ligand failed to block reconsolidation of object recognition memory (ORM) whereas β1AR selective antagonists completely suppressed the ORM reconsolidation |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Biased ligand suppressed memory reactivation-induced cAMP levels |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Biased ligand did not affect memory reactivation-induced ERK levels |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7158
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
alprenolol
|
β-arrestin |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Biased ligand failed to block reconsolidation of object recognition memory (ORM) |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
β-arrestin 2 played a key role in ORM reconsolidation whereas biased ligand failed to restore ORM reconsolidation in β-arrestin 2 knock out mice |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
9961
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
(-)-propranolol
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Ablation of β-arrestin 2 or antagonist treatment abolished memory re-activation induced ERK activation |
Knock out of sig. prot. |
Animals |
Histological examination |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7409
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
betaxolol
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Ablation of β-arrestin 2 or antagonist treatment abolished memory re-activation induced de novo protein synthesis |
Knock out of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Rescued β-arrestin 2 expression in knock-out mice restored pERK levels post memory reactivation |
Knock out of sig. prot. |
Animals |
Histological examination |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7409
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
betaxolol
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation |
Rescued β-arrestin 2 expression in knock-out mice restored ORM reconsolidation |
Knock out of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
Pharmalogical disruption of memory reconsolidation could help in treating drug addiction |
Biased ligand increased re-activation of cocaine-induced conditioned place preference (CPP) memory compared to antagonist |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7590
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
carvedilol
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
Pharmalogical disruption of memory reconsolidation could help in treating drug addiction |
Biased ligand increased re-activation of freezing behaviour in contextual fear memory test as compared to antagonist |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
7158
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
alprenolol
|
β-arrestin-2 |
|
Psychiatric disorder |
Memory retention |
Pharmalogical disruption of memory reconsolidation could help in treating fear-related disorders |
Biased ligand increased re-activation of freezing behaviour in contextual fear memory test as compared to antagonist |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L |
112:4483-8 |
178565
|
A |
Dopamine receptors |
DRD2 |
D2 |
Human |
CHEMBL4467883
|
β-arrestin |
|
Psychiatric disorder |
Neuroprotection |
Biased antagonist helps in suppressing D2R/β-arrestin 2 signalling mediated hyperactivity behaviours |
Biased ligand shows potent antagonistic activity for β-arrestin recruitment whereas no antagonistic activity seen for the Gi/cAMP pathway |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Weiwer M, Xu Q, Gale JP, Lewis M, Campbell AJ, Schroeder FA, Van de Bittner GC, Walk M, Amaya A, Su P, D Ordevic L, Sacher JR, Skepner A, Fei D, Dennehy K, Nguyen S, Faloon PW, Perez J, Cottrell JR, Liu F, Palmer M, Pan JQ, Hooker JM, Zhang YL, Scolnick E, Wagner FF, Holson EB |
13:1038-1047 |
178565
|
A |
Dopamine receptors |
DRD2 |
D2 |
Human |
CHEMBL4467883
|
β-arrestin |
|
Psychiatric disorder |
Neuroprotection |
Biased antagonist helps in suppressing D2R/β-arrestin 2 signalling mediated hyperactivity behaviours |
Biased ligand restored levels of pGSK3⍺ (Ser21/9) indicating lack of β-arrestin signalling |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Weiwer M, Xu Q, Gale JP, Lewis M, Campbell AJ, Schroeder FA, Van de Bittner GC, Walk M, Amaya A, Su P, D Ordevic L, Sacher JR, Skepner A, Fei D, Dennehy K, Nguyen S, Faloon PW, Perez J, Cottrell JR, Liu F, Palmer M, Pan JQ, Hooker JM, Zhang YL, Scolnick E, Wagner FF, Holson EB |
13:1038-1047 |
178565
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
CHEMBL4467883
|
β-arrestin |
|
Psychiatric disorder |
Neuroprotection |
Biased antagonist helps in suppressing D2R/β-arrestin 2 signalling mediated hyperactivity behaviours |
Biased ligand showed reduced activity in amphetamine-induced hyperlocomotion (AIH) |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Weiwer M, Xu Q, Gale JP, Lewis M, Campbell AJ, Schroeder FA, Van de Bittner GC, Walk M, Amaya A, Su P, D Ordevic L, Sacher JR, Skepner A, Fei D, Dennehy K, Nguyen S, Faloon PW, Perez J, Cottrell JR, Liu F, Palmer M, Pan JQ, Hooker JM, Zhang YL, Scolnick E, Wagner FF, Holson EB |
13:1038-1047 |
178565
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
CHEMBL4467883
|
β-arrestin |
|
Psychiatric disorder |
Neuroprotection |
Biased antagonist helps in suppressing D2R/β-arrestin 2 signalling mediated hyperactivity behaviours while avoiding side effect of motoric impairment |
Biased ligand showed reduced motoric side-effects in rotarod model |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Weiwer M, Xu Q, Gale JP, Lewis M, Campbell AJ, Schroeder FA, Van de Bittner GC, Walk M, Amaya A, Su P, D Ordevic L, Sacher JR, Skepner A, Fei D, Dennehy K, Nguyen S, Faloon PW, Perez J, Cottrell JR, Liu F, Palmer M, Pan JQ, Hooker JM, Zhang YL, Scolnick E, Wagner FF, Holson EB |
13:1038-1047 |
226075
|
A |
Dopamine receptors |
DRD2 |
D2 |
Human |
16c
|
gαoa |
|
Psychiatric disorder |
Neuroprotection |
Biased agonist helps in suppressing hyperactivity behaviours |
Biased ligand displayed partial agonism towards G-protein signalling whereas β-arrestin 2 recruitment was absent |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Wang X, Zhang X, Zhang M, Zhang Q, Dong P, Ding H, Liu X |
9:37417 |
226075
|
A |
Dopamine receptors |
DRD2 |
D2 |
Human |
16c
|
gαoa |
|
Psychiatric disorder |
Neuroprotection |
Biased agonist promoted activation of G-protein/GIRK channel helps in regulating nociception, reward-related behaviour, cognition, mood and heart-rate regulation |
Biased agnoist stimulated G-protein dependent acitvation of GIRK channel |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Wang X, Zhang X, Zhang M, Zhang Q, Dong P, Ding H, Liu X |
9:37417 |
226075
|
A |
Dopamine receptors |
DRD2 |
D2 |
Rat |
16c
|
gαoa |
|
Psychiatric disorder |
Neuroprotection |
Biased agonist helps in suppressing hyperactivity behaviours |
Biased ligand displayed reduced hyper-locomotary tendency in amphetamine-induced schizoprenia-like behaviour in rats |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Wang X, Zhang X, Zhang M, Zhang Q, Dong P, Ding H, Liu X |
9:37417 |
10015
|
A |
Apelin receptors |
APJ |
apelin |
Rat |
[Pyr1]apelin-13
|
g protein |
|
Heart disease |
Cardioprotection |
Apelin stimulated APJ signalling affected by stretch leads to less effective G-protein signalling whereas β-arrestin recruitment/signalling is robust |
Apelin stimulation reduced hypertrophy marker ANF (Atrial Natriuretic Factor) in stretched cardiomyocytes whereas elevated ANF levels seen in apelin stimulated/PTX-tretaed stretched cardiomyocytes |
Downstream inhibition of sig. pathway |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Scimia MC, Hurtado C, Ray S, Metzler S, Wei K, Wang J, Woods CE, Purcell NH, Catalucci D, Akasaka T, Bueno OF, Vlasuk GP, Kaliman P, Bodmer R, Smith LH, Ashley E, Mercola M, Brown JH, Ruiz-Lozano P |
488:394-8 |
10015
|
A |
Apelin receptors |
APJ |
apelin |
Rat |
[Pyr1]apelin-13
|
β-arrestin |
|
Heart disease |
Cardioprotection |
β-arrestin mediated receptor signalling plays a major role in stretch-induced myocardial hypertrophy |
β-arrestin knockdown led to reduced levels of hypertrophy marker β-MHC (Myosin Heavy Chain) in stretched cardiomyocytes |
Gene silencing (siRNA) of sig. prot. |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Scimia MC, Hurtado C, Ray S, Metzler S, Wei K, Wang J, Woods CE, Purcell NH, Catalucci D, Akasaka T, Bueno OF, Vlasuk GP, Kaliman P, Bodmer R, Smith LH, Ashley E, Mercola M, Brown JH, Ruiz-Lozano P |
488:394-8 |
9359
|
A |
Apelin receptors |
APJ |
apelin |
Human |
MM07
|
g protein |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Ligand showed bias towards G-protein signalling whereas β-arrestin recruitment and internalisation was less potent |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP |
65:834-40 |
9359
|
A |
Apelin receptors |
APJ |
apelin |
Rat |
MM07
|
g protein |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Biased ligand promoted dose-dependent increase in cardiac output without affecting heart rate and respiratory rate |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP |
65:834-40 |
9359
|
A |
Apelin receptors |
APJ |
apelin |
Rat |
MM07
|
g protein |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Biased ligand promoted an increase in peak velocity across left ventricular outflow |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP |
65:834-40 |
9359
|
A |
Apelin receptors |
APJ |
apelin |
Human |
MM07
|
g protein |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Biased ligand promoted an increase in forearm bloodflow (FBF) in human volunteers |
Biased ligand (towards sig. prot.) |
Humans |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP |
65:834-40 |
9359
|
A |
Apelin receptors |
APJ |
apelin |
Human |
MM07
|
g protein |
|
Heart disease |
Cardioprotection |
Bias towards G-protein signalling over β-arrestin signalling helps in reducing receptor downregulation thereby aiding in cardioprotective activity of the ligand |
Biased ligand reversed norepinephrine mediated vasoconstriction in human volunteers |
Biased ligand (towards sig. prot.) |
Humans |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP |
65:834-40 |
8280
|
B1 |
Parathyroid hormone receptors |
PTH1R |
PTH1 |
Mouse |
[D-Trp12,Tyr34]PTH-(7-34) (bovine)
|
β-arrestin-2 |
|
Endocrine system disease |
Bone formation |
Bone formation physiology is partly dependent on PTH1R-β-arrestin signalling pathway |
Biased ligand failed to stimulate cAMP formation whereas robustly stimulated ERK activation through β-arrestin dependent signaling pathway |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Gesty-Palmer D, Flannery P, Yuan L, Corsino L, Spurney R, Lefkowitz RJ, Luttrell LM |
1:1ra1 |
8280
|
B1 |
Parathyroid hormone receptors |
PTH1R |
PTH1 |
Mouse |
[D-Trp12,Tyr34]PTH-(7-34) (bovine)
|
β-arrestin-2 |
|
Endocrine system disease |
Bone formation |
Bone formation physiology is partly dependent on PTH1R-β-arrestin signalling pathway |
Biased ligand suppressed basal cAMP production and failed to stimulate ERK activation in β-arrestin 2 knockout cells |
Knock out of sig. prot. |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Gesty-Palmer D, Flannery P, Yuan L, Corsino L, Spurney R, Lefkowitz RJ, Luttrell LM |
1:1ra1 |
8280
|
B1 |
Parathyroid hormone receptors |
PTH1R |
PTH1 |
Mouse |
[D-Trp12,Tyr34]PTH-(7-34) (bovine)
|
β-arrestin-2 |
|
Endocrine system disease |
Bone formation |
Bone formation physiology is partly dependent on PTH1R-β-arrestin signalling pathway |
Biased ligand failed to promote lumbar spine bone mineral deposition (BMD) in the β-arrestin 2 knockout mice |
Knock out of sig. prot. |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Gesty-Palmer D, Flannery P, Yuan L, Corsino L, Spurney R, Lefkowitz RJ, Luttrell LM |
1:1ra1 |
8280
|
B1 |
Parathyroid hormone receptors |
PTH1R |
PTH1 |
Mouse |
[D-Trp12,Tyr34]PTH-(7-34) (bovine)
|
β-arrestin-2 |
|
Endocrine system disease |
Bone formation |
Bone formation physiology is partly dependent on PTH1R-β-arrestin signalling pathway |
Biased ligand failed to promote lumbar as well as proximal tibial trabecular bone formation in β-arrestin 2 knockout cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Gesty-Palmer D, Flannery P, Yuan L, Corsino L, Spurney R, Lefkowitz RJ, Luttrell LM |
1:1ra1 |
8280
|
B1 |
Parathyroid hormone receptors |
PTH1R |
PTH1 |
Mouse |
[D-Trp12,Tyr34]PTH-(7-34) (bovine)
|
β-arrestin-2 |
|
Endocrine system disease |
Bone formation |
Bone formation physiology is partly dependent on PTH1R-β-arrestin signalling pathway |
Biased ligand failed to promote osteoblastic activity in β-arrestin 2 knockout cells weheras the osteoclastic activity was completely dependent on G-protein signalling |
Knock out of sig. prot. |
Animals |
Histological examination |
Gesty-Palmer D, Flannery P, Yuan L, Corsino L, Spurney R, Lefkowitz RJ, Luttrell LM |
1:1ra1 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Ligand showed bias towards G-protein signalling whereas β-arrestin recruitment and subsequent desensitisation was absent |
Biased ligand (towards sig. prot.) |
Cells |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand performed better in glucose tolerance test (GTT) over full agonist at lower concentrations in normal lean mice |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand showed similar effects in glucose tolerance test (GTT) compared to full agonist in diabetic ob/ob mice. However, biased ligand slightly underperformed compared to reference ligand in insulin resistant diet-induced obese (DIO) mice |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand is a weak insulin secretagouge as compared to reference ligand thereby hinting its β-cell independent glucoregulatory activity |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand displayed better anti-hyperglycaemic activity as compared to reference ligand in diabetic ob/ob mice |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand displayed better anti-hyperglycaemic activity at lower concentrations as compared to reference ligand in insulin resistant diet-induced obese (DIO) mice |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand showed highest decrease in HbA1c levels at both tested concentrations in insulin resistant DIO mice |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand robustly elevated GIP (Glucose-dependent insulinotropic polypeptide) levels as compared to reference ligand thereby indicating it's β-cell independent glucoregulatory activity |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand decreased adipose-tissue secreted resistin levels whereas reference ligand failed to reduce resistin levels in DIO mice |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand elevated PPAR𝛄-regulated CD36 levels in eWAT (Epididymal White Adipose Tissue) of DIO mice. Alternatively, full agonist failed to do so, thereby indicating that biased and full agonist affect PPAR𝛄 activity in different ways |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
226076
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
P5
|
g protein |
|
Metabolic or nutritional disease |
Anti-diabetic |
Biased ligand showed better anti-diabetic effects as compared to conventional full agonist |
Biased ligand treatment showed smaller and increased number of adipocytes as compared to reference ligand in DIO mice |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA |
6:8918 |
7207
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
angiotensin II
|
gαq11 |
|
Heart disease |
Cardioprotection |
G protein-dependent ERK1/2 activation can reasult to hypertrophic growth of cardiac myocytes. |
Relative myocyte size was larger in Angiotensin II-stimulated myocytes than in (SII)AngII-stimulated myocytes and control. The effect could be blocked by Telmisartan. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Aplin M, Christensen GL, Schneider M, Heydorn A, Gammeltoft S, Kjolbye AL, Sheikh SP, Hansen JL |
100:296-301 |
226077
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
[Sar1, Ile4, Ile8]-AngII
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
β-arrestin-2-dependent stimulation of ERK1/2 can result in proliferation of cardiac myocytes. |
(SII)AngII induced DNA synthesis and proliferation in myocytes. This effect was reduced by the application of telmisartan. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Aplin M, Christensen GL, Schneider M, Heydorn A, Gammeltoft S, Kjolbye AL, Sheikh SP, Hansen JL |
100:296-301 |
10649
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
TRV027
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
Biased ligand towards β-arrestin decreased the blood pressure while increasing cardiac performance. |
Cardiomyocytes from mice, that were treated with the biased ligand showed an increase in cell contractility, that was absent under treatment with valsartan. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Violin JD, DeWire SM, Yamashita D, Rominger DH, Nguyen L, Schiller K, Whalen EJ, Gowen M, Lark MW |
335:572-9 |
10649
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
TRV027
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
Biased ligand towards β-arrestin decreased the blood pressure while increasing cardiac performance. |
Rats, that were treated with the biased ligand and then challenged with eight doses of angiotensin II, showed a decrease in blood pressure compared to vehicle and or losartan. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Violin JD, DeWire SM, Yamashita D, Rominger DH, Nguyen L, Schiller K, Whalen EJ, Gowen M, Lark MW |
335:572-9 |
10649
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
TRV027
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
Biased ligand towards β-arrestin decreased the blood pressure while increasing cardiac performance. |
Cordiomyocytes from rats, that were treated with the biased ligand and then challenged with eight doses of angiotensin II, showed an increase in cell contractility that was absent under treatment with losartan. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Violin JD, DeWire SM, Yamashita D, Rominger DH, Nguyen L, Schiller K, Whalen EJ, Gowen M, Lark MW |
335:572-9 |
10649
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
TRV027
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
Biased ligand towards β-arrestin decreased the blood pressure while increasing cardiac performance. |
Unlike telmisartan, the biased ligand increased cardiac contractility and showed a preservation of stroke volume in left ventricular PV loop analysis in rats. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Violin JD, DeWire SM, Yamashita D, Rominger DH, Nguyen L, Schiller K, Whalen EJ, Gowen M, Lark MW |
335:572-9 |
164310
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
TROGLITAZONE
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
Biased ligand stimulated cardiomyocyte contractility via β-arrestin. |
Biased ligand resulted in a significant increase in percentage and rate of cell shortening in isolated murine cardiomyocytes. This effect was blocked by pretreatment with valsartan and absent in β-arrestin knockout mice myocytes. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Tilley DG, Nguyen AD, Rockman HA |
396:921-6 |
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
-
|
β-arrestin-2 |
|
Heart disease |
Cardioprotection |
Biased ligand stimulated cardiomyocyte contractility via β-arrestin. |
Wild type cardiomyocytes showed a higher % change in contractility under treatment with angiotensin II and Troglitazone than β-arrestin knockout cardiomyocytes. |
Knock out of sig. prot. |
Animals |
Histological examination |
Tilley DG, Nguyen AD, Rockman HA |
396:921-6 |
|
A |
Melanocortin receptors |
MC4R |
MC4 |
Human |
-
|
β-arrestin-2 |
|
Metabolic or nutritional disease |
Anti-obesity |
β-arrestin biased signaling might be helpful in weight loss and treatment of obesity-related cardiometabolic diseases. |
Gene variants, that showed a natural bias, were associated with a significant lower Body Mass Index, based on data of European ancestry participants from UK Biobank. |
naturally occuring receptor variants |
Humans |
Genetic association study |
Lotta LA, Mokrosinski J, Mendes de Oliveira E, Li C, Sharp SJ, Luan J, Brouwers B, Ayinampudi V, Bowker N, Kerrison N, Kaimakis V, Hoult D, Stewart ID, Wheeler E, Day FR, Perry JRB, Langenberg C, Wareham NJ, Farooqi IS |
177:597-607.e9 |
|
A |
Melanocortin receptors |
MC4R |
MC4 |
Human |
-
|
β-arrestin-2 |
|
Metabolic or nutritional disease |
Anti-obesity |
β-arrestin biased signaling might be helpful in weight loss and treatment of obesity-related cardiometabolic diseases. |
Gene variants that, showed a natural bias, were associated with up to 50% lower risk of obesity, based on data of European ancestry participants from UK Biobank. |
naturally occuring receptor variants |
Humans |
Genetic association study |
Lotta LA, Mokrosinski J, Mendes de Oliveira E, Li C, Sharp SJ, Luan J, Brouwers B, Ayinampudi V, Bowker N, Kerrison N, Kaimakis V, Hoult D, Stewart ID, Wheeler E, Day FR, Perry JRB, Langenberg C, Wareham NJ, Farooqi IS |
177:597-607.e9 |
|
A |
Melanocortin receptors |
MC4R |
MC4 |
Human |
-
|
β-arrestin-2 |
|
Metabolic or nutritional disease |
Anti-diabetic |
β-arrestin biased signaling might be helpful in weight loss and treatment of obesity-related cardiometabolic diseases. |
Gene variants, that showed a natural bias, were associated with up to 50% lower risk of type 2 diabetes, based on data of European ancestry participants from UK Biobank. |
naturally occuring receptor variants |
Humans |
Genetic association study |
Lotta LA, Mokrosinski J, Mendes de Oliveira E, Li C, Sharp SJ, Luan J, Brouwers B, Ayinampudi V, Bowker N, Kerrison N, Kaimakis V, Hoult D, Stewart ID, Wheeler E, Day FR, Perry JRB, Langenberg C, Wareham NJ, Farooqi IS |
177:597-607.e9 |
|
A |
Melanocortin receptors |
MC4R |
MC4 |
Human |
-
|
β-arrestin-2 |
|
Metabolic or nutritional disease |
Cardioprotection |
β-arrestin biased signaling might be helpful in weight loss and treatment of obesity-related cardiometabolic diseases. |
Gene variants, that showed a natural bias, were associated with up to 50% lower risk of coronary artery disease, based on data of European ancestry participants from UK Biobank. |
naturally occuring receptor variants |
Humans |
Genetic association study |
Lotta LA, Mokrosinski J, Mendes de Oliveira E, Li C, Sharp SJ, Luan J, Brouwers B, Ayinampudi V, Bowker N, Kerrison N, Kaimakis V, Hoult D, Stewart ID, Wheeler E, Day FR, Perry JRB, Langenberg C, Wareham NJ, Farooqi IS |
177:597-607.e9 |
|
A |
Hydroxycarboxylic acid receptors |
HCAR2 |
HCA2 |
Mouse |
-
|
β-arrestin-1 |
|
Metabolic or nutritional disease |
adverse effect of nicotinic acid |
Nicotinic acid decreases free fatty acid levels through G protein signaling, while cutaneous flushing is mediated by β-arrestin1 and might be partially mediated by β-arrestin2. |
The perfusion of the ventral ear in β-arrestin1 knockout mice was lower compared to wild type mice. |
Knock out of sig. prot. |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Walters RW, Shukla AK, Kovacs JJ, Violin JD, DeWire SM, Lam CM, Chen JR, Muehlbauer MJ, Whalen EJ, Lefkowitz RJ |
119:1312-21 |
|
A |
Hydroxycarboxylic acid receptors |
HCAR2 |
HCA2 |
Mouse |
-
|
gi/o-family |
|
Metabolic or nutritional disease |
antilipolysis |
Nicotinic acid decreases free fatty acid levels through G protein signaling, while cutaneous flushing is mediated by β-arrestin1 and might be partially mediated by β-arrestin2. |
Nicotinic acid decreased the level of free fatty acids in wild-type, β-arrestin1-, and β-arrestin2-knockout mice. |
Knock out of sig. prot. |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Walters RW, Shukla AK, Kovacs JJ, Violin JD, DeWire SM, Lam CM, Chen JR, Muehlbauer MJ, Whalen EJ, Lefkowitz RJ |
119:1312-21 |
|
A |
Hydroxycarboxylic acid receptors |
HCAR2 |
HCA2 |
Mouse |
-
|
β-arrestin-2 |
|
Metabolic or nutritional disease |
adverse effect of nicotinic acid |
Nicotinic acid decreases free fatty acid levels through G protein signaling, while cutaneous flushing is mediated by β-arrestin1 and might be partially mediated by β-arrestin2. |
There was a nonsignificant trend towards diminished cutaneous flushing in β-arrestin2 knockout mice, compared to wild type mice. |
Knock out of sig. prot. |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Walters RW, Shukla AK, Kovacs JJ, Violin JD, DeWire SM, Lam CM, Chen JR, Muehlbauer MJ, Whalen EJ, Lefkowitz RJ |
119:1312-21 |
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
-
|
β-arrestin-1 |
|
Metabolic or nutritional disease |
antiapoptotic |
β-arrestin1 plays an important role in the GLP-1-mediated antiapoptotic effect under high glucose exposure. |
β-arrestin1 knockdown cells showed lower levels of cleaved caspase-3 under prolonged high glucose exposure and GLP-1 treatment compared to control siRNA-transfected cells. |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Quoyer J, Longuet C, Broca C, Linck N, Costes S, Varin E, Bockaert J, Bertrand G, Dalle S |
285:1989-2002 |
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Mouse |
-
|
β-arrestin-1 |
|
Metabolic or nutritional disease |
antiapoptotic |
β-arrestin1 plays an important role in the GLP-1-mediated antiapoptotic effect under high glucose exposure. |
Pancreatic islets with a β-arrestin1 knock out showed a ~2-fold increase in DNA fragmentation under high glucose exposure compared to will type cells. |
Knock out of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Quoyer J, Longuet C, Broca C, Linck N, Costes S, Varin E, Bockaert J, Bertrand G, Dalle S |
285:1989-2002 |
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Rat |
-
|
β-arrestin-1 |
|
Metabolic or nutritional disease |
Anti-diabetic |
β-arrestin1 mediates GLP-1 induced insulin secretion. |
The addition of GLP-1 led to a significant increase in insulin secretion, which was inhibited by β-arrestin1 knockdown. |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Sonoda N, Imamura T, Yoshizaki T, Babendure JL, Lu JC, Olefsky JM |
105:6614-9 |
|
B1 |
Glucagon receptor family |
GLP1R |
GLP-1 |
Rat |
-
|
β-arrestin-1 |
|
Metabolic or nutritional disease |
anti-diabetic |
β-arrestin1 mediates GLP-1 induced insulin secretion. |
GLP-1 stimulation led to a rapid phosphorylation of CREB and ERK1/2 which was attenuated in β-arrestin 1 knockdown cells. GLP-1 stimulation led to a time-dependent increase in IRS-2 protein levels and IRS-2 expression levels were down-regulated in β-arrestin 1 knockdown cells. |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Sonoda N, Imamura T, Yoshizaki T, Babendure JL, Lu JC, Olefsky JM |
105:6614-9 |
7205
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
angiotensin-(1-7)
|
β-arrestin |
|
Heart disease |
Cardioprotection |
Ang(1-7) has a cardioprotective effect concerning the development of cardiac hypertrophy via β-arrestin signaling. |
Treatment with biased ligand and isoprotenerol led to a partial blockage of the developmentn of cardiac hypertrophy. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Teixeira LB, Parreiras-E-Silva LT, Bruder-Nascimento T, Duarte DA, Simoes SC, Costa RM, Rodriguez DY, Ferreira PAB, Silva CAA, Abrao EP, Oliveira EB, Bouvier M, Tostes RC, Costa-Neto CM |
7:11903 |
7205
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
angiotensin-(1-7)
|
β-arrestin |
|
Heart disease |
Cardioprotection |
Ang(1-7) has a cardioprotective effect concerning the development of cardiac hypertrophy via β-arrestin signaling. |
Treatment with biased ligand and isoprotenerol led to a complete prevention of the increase in end diastolic pressure (EDP). |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Teixeira LB, Parreiras-E-Silva LT, Bruder-Nascimento T, Duarte DA, Simoes SC, Costa RM, Rodriguez DY, Ferreira PAB, Silva CAA, Abrao EP, Oliveira EB, Bouvier M, Tostes RC, Costa-Neto CM |
7:11903 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Human |
-
|
g12/13-family |
side effects (deleterious bleeding) of anti-thrombin agents |
|
Cardioprotection |
Thrombin induces changes in barrier permeability via Gα12/13 and calcium-mobilization via Gαq. |
Inhibition of Rho kinase showed that thrombin-induced changes in barrier permeability are dependent upon Gα12/13 |
Downstream inhibition of sig. pathway |
Humans |
Histological examination |
McLaughlin JN, Shen L, Holinstat M, Brooks JD, Dibenedetto E, Hamm HE |
280:25048-59 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Human |
-
|
gαq |
side effects (deleterious bleeding) of anti-thrombin agents |
|
Cardioprotection |
Thrombin induces changes in barrier permeability via Gα12/13 and calcium-mobilization via Gαq. |
Inhibition of PLC-β and Gαi/o showed that Calcium-mobilization is dependet on PLC-β activation via Gαq. |
Downstream inhibition of sig. pathway |
Humans |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
McLaughlin JN, Shen L, Holinstat M, Brooks JD, Dibenedetto E, Hamm HE |
280:25048-59 |
|
A |
Hydroxycarboxylic acid receptors |
HCAR1 |
HCA1 |
Mouse |
-
|
giɑ |
|
Nervous system disease |
antiepileptic |
HCAR1 mediates a decrease of neuronal excitabilty through Giα signaling which can lead to down-modulation of neuronal activity. |
HCAR1 mediates a decrease of neuronal excitabilty through Giα signaling. |
Downstream inhibition of sig. pathway |
Animals |
Histological examination |
de Castro Abrantes H, Briquet M, Schmuziger C, Restivo L, Puyal J, Rosenberg N, Rocher AB, Offermanns S, Chatton JY |
39:4422-4433 |
226078
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
Cathepsin S
|
gαs |
inflammatory disease like rheumatoid arthritis and colitis |
|
inflammatory pain |
Cat-S is a biased agonist of PAR2-dependent inflammation and pain. |
Biased ligand induced hyperexcitability of nociceptive neurons. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on excised organ/tissue/slice |
Zhao P, Lieu T, Barlow N, Metcalf M, Veldhuis NA, Jensen DD, Kocan M, Sostegni S, Haerteis S, Baraznenok V, Henderson I, Lindstrom E, Guerrero-Alba R, Valdez-Morales EE, Liedtke W, McIntyre P, Vanner SJ, Korbmacher C, Bunnett NW |
289:27215-27234 |
226078
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
Cathepsin S
|
gαs |
inflammatory disease like rheumatoid arthritis and colitis |
|
inflammatory pain |
Cat-S is a biased agonist of PAR2-dependent inflammation and pain. |
Biased ligand induced mechanical hyperalgesia which was measured by paw withdrawal. Ligand was administrated itraplantar and hyperalgesia was measured using calibrated von Frey filaments. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Zhao P, Lieu T, Barlow N, Metcalf M, Veldhuis NA, Jensen DD, Kocan M, Sostegni S, Haerteis S, Baraznenok V, Henderson I, Lindstrom E, Guerrero-Alba R, Valdez-Morales EE, Liedtke W, McIntyre P, Vanner SJ, Korbmacher C, Bunnett NW |
289:27215-27234 |
226078
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
Cathepsin S
|
gαs |
inflammatory disease like rheumatoid arthritis and colitis |
|
inflammatory pain |
Cat-S is a biased agonist of PAR2-dependent inflammation and pain. |
Biased ligand induced inflammatory edema. Paw thickness was measured using a caliper after intraplantar injection of ligand. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Zhao P, Lieu T, Barlow N, Metcalf M, Veldhuis NA, Jensen DD, Kocan M, Sostegni S, Haerteis S, Baraznenok V, Henderson I, Lindstrom E, Guerrero-Alba R, Valdez-Morales EE, Liedtke W, McIntyre P, Vanner SJ, Korbmacher C, Bunnett NW |
289:27215-27234 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
analgesia |
Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. |
TRV130 induced rapid and powerful analgesia in mouse hot plate study. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD |
344:708-17 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Rat |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
analgesia |
Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. |
TRV130 induced rapid and powerful analgesia in rat hot plate, tail flick, and incisional pain study. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD |
344:708-17 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
OLICERIDINE
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. |
TRV130 induced less gastrointestinal dysfunction than morphine at equivalent doses in mouse glass bead colonic motility and fecal boli assay. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD |
344:708-17 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Rat |
OLICERIDINE
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. |
TRV130 induced less gastrointestinal dysfunction than morphine at equivalent doses in rat glass bead colonic motility and fecal boli assay. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD |
344:708-17 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Rat |
OLICERIDINE
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. |
TRV130 showed increased analgesia vs. Respiratory suppression and sedation in rat arterial blood gas measurement. |
Biased ligand (towards sig. prot.) |
Animals |
Blood analysis |
DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD |
344:708-17 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
analgesia |
TRV130 produced significantly greater categorical pain relief than morphine after first dose, no serious adverse effects and tolerability similar to morphine. |
Biased ligand showed significant reduction of pain intensity over 49 hours compared with placebo |
Biased ligand (towards sig. prot.) |
Humans |
Numeric rating scales (pain intensity, etc.) |
Viscusi ER, Webster L, Kuss M, Daniels S, Bolognese JA, Zuckerman S, Soergel DG, Subach RA, Cook E, Skobieranda F |
157:264-272 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
TRV130 produced significantly greater categorical pain relief than morphine after first dose, no serious adverse effects and tolerability similar to morphine. |
Biased ligand showed dose-related opioid related adverse effects, most commonly nausea, dizziness, headache, and vomiting. |
Biased ligand (towards sig. prot.) |
Humans |
Open-ended questions (report of AEs) |
Viscusi ER, Webster L, Kuss M, Daniels S, Bolognese JA, Zuckerman S, Soergel DG, Subach RA, Cook E, Skobieranda F |
157:264-272 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
analgesia |
TRV130 provides rapid analgesia compared to placebo and has a favorable sefety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. |
Biased ligand provides rapid analgesia for the relief of moderate-to-severe acute postoperative pain. |
Biased ligand (towards sig. prot.) |
Humans |
Numeric rating scales (pain intensity, etc.) |
Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N |
12:927-943 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
TRV130 provides rapid analgesia compared to placebo and has a favorable sefety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. |
Biased ligand showed significant lower odds ratio for antiemetic use in TRV130 regimes compared to morphine. |
Biased ligand (towards sig. prot.) |
Humans |
Use of rescue medication (e.g. antiemetic or pain meds) |
Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N |
12:927-943 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
TRV130 provides rapid analgesia compared to placebo and has a favorable sefety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. |
Biased ligand showed favorable safety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. |
Biased ligand (towards sig. prot.) |
Humans |
Physical examination |
Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N |
12:927-943 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
g protein |
opioid analgesia and side effects |
|
analgesia |
Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. |
Phosphorylation-deficient MOR mice showed an increase of analgesic potency of opioids in hot plate studies. |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S |
10:367 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
g protein |
opioid analgesia and side effects |
|
side effects of opioids |
Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. |
Opioids induced respiratory depression in all mutant receptor mice measured by plethysmography. |
Knock in - mutant receptor with impared signalling |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S |
10:367 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
g protein |
opioid analgesia and side effects |
|
side effects of opioids |
Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. |
Opioids induced constipation in all mutant receptor mice measured by accumulated fecal boli quantification. |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S |
10:367 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
g protein |
opioid analgesia and side effects |
|
side effects of opioids |
Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. |
Mice display typical signs of withdrawal including jumping, wet-dog shakes and grooming with no significant difference between receptor phenotypes. Observation of behavior followed naloxone injection. |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S |
10:367 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
β-arrestin |
opioid analgesia and side effects |
|
side effects of opioids |
Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. |
Desensitization of MOR coupling to GIRK channels in locus coeruleus neurons from horizontal brain sections of mice from all receptor genotypes. |
Knock in - mutant receptor with impared signalling |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S |
10:367 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
β-arrestin |
opioid analgesia and side effects |
|
side effects of opioids |
Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. |
Mutant receptor mice show no significant shift in sensitivity in hot plate study after 7 days of constant opioid exposure. |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S |
10:367 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
gi/o-family |
opioid analgesia and side effects |
|
analgesia |
PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. |
Biased ligand shows analgesia (specific for central over reflex analgesia) in mice hot plate, tail-flick and formalin injection studies. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK |
537:185-190 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. |
Biased ligand showed no apparent respiratory depression in whole-body plethysmography. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK |
537:185-190 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. |
Biased ligands did not show hyperlocomotion in an open field assay. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK |
537:185-190 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
β-arrestin-2 (non-visual arrestin-3) |
opioid analgesia and side effects |
|
side effects of opioids |
PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. |
Biased ligand did not induce conditioned place preference in mice. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK |
537:185-190 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
analgesia |
Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. |
Biased ligand showed antinociception without tolerance development in tail-withdrawal study. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS |
31:730-739 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
side effects of opioids |
Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. |
Biased ligand showed suppression of fecal output without tolerance development in fecal boli accumulation assay. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS |
31:730-739 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
side effects of opioids |
Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. |
Biased ligand nearly eliminated colonic propulsion which was measured by video imaging with a gastrointestinal motility monitor system. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS |
31:730-739 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Rat |
OLICERIDINE
|
g protein |
opioid analgesia and side effects |
|
side effects of opioids |
Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. |
Biased ligand might induce physical dependence and addiction which was measured in intracranial self stimulation studies. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS |
31:730-739 |
226079
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
TRV120023
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
Cardioprotection |
Biased ligand promotes cell survival during acute cardiac injury. |
Biased ligand increased cardiac contractility in pressure colume loop analysis in wild type and β-arrestin2 knock out mice after bilateral vagotomy and artificial increase of the afterload. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Kim KS, Abraham D, Williams B, Violin JD, Mao L, Rockman HA |
303:H1001-10 |
226079
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
TRV120023
|
g protein |
|
Heart disease |
cardiotoxic effect |
Biased ligand promotes cell survival during acute cardiac injury. |
Biased ligand reduced left ventricle systolic pressure in wild type and β-arrestin2 knock out mice after bilateral vagotomy and artificial increase of the afterload. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Kim KS, Abraham D, Williams B, Violin JD, Mao L, Rockman HA |
303:H1001-10 |
226079
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
TRV120023
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
Cardioprotection |
Biased ligand promotes cell survival during acute cardiac injury. |
Biased ligand enhanced cardioprotective ERK1/2 and Akt signaling in myocardial lysates after ischemia reperfusion injury of wild type and β-arrestin2 knock out mice with pretreatment of TRV120023. |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Kim KS, Abraham D, Williams B, Violin JD, Mao L, Rockman HA |
303:H1001-10 |
226079
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
TRV120023
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
Cardioprotection |
Biased ligand promotes cell survival during acute cardiac injury. |
Biased ligand reduced the number of TUNEL-positive cardiomyocytes (marker of apoptosis) in myocardial lysates after ischemia reperfusion injury of wild type and β-arrestin2 knock out mice with pretreatment of TRV120023. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Kim KS, Abraham D, Williams B, Violin JD, Mao L, Rockman HA |
303:H1001-10 |
226079
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Mouse |
TRV120023
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
Cardioprotection |
Biased ligand promotes cell survival during acute cardiac injury. |
Biased ligand reduced the number of TUNEL-positive cardiomyocytes (marker of apoptosis) in myocardial stretch injury ex vivo of wild type and β-arrestin2 knock out mice. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Kim KS, Abraham D, Williams B, Violin JD, Mao L, Rockman HA |
303:H1001-10 |
226079
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
TRV120023
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
Cardioprotection |
Biased ligand inhibits angiotensin II-induced cardiac hypertrophy while preserving contractility. |
Biased ligand attenuated prohypertrophic effects which was measured through echocardiography in a hypertrophic rat model. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Monasky MM, Taglieri DM, Henze M, Warren CM, Utter MS, Soergel DG, Violin JD, Solaro RJ |
305:H856-66 |
226079
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
TRV120023
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
Cardioprotection |
Biased ligand inhibits angiotensin II-induced cardiac hypertrophy while preserving contractility. |
Biased ligand preserved cardiac contractility which was measured by myofilament Calcium responsiveness in a hypertrophic rat model. |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Monasky MM, Taglieri DM, Henze M, Warren CM, Utter MS, Soergel DG, Violin JD, Solaro RJ |
305:H856-66 |
226080
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
[SII]AngII
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
Cardioprotection |
Biased receptor activation reduces ischemia reperfusion injury of the heart. |
Preconditioning with biased ligand significantly reduced infarct size. |
Biased ligand (towards sig. prot.) |
Animals |
Histological examination |
Hostrup A, Christensen GL, Bentzen BH, Liang B, Aplin M, Grunnet M, Hansen JL, Jespersen T |
30:642-52 |
7207
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
angiotensin II
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
antiapoptotic |
β-arrestin2 mediates anti-apoptotic signaling through regulation of BAD phosphorylation. |
Protection from caspase-dependent apoptotic process in cleaved caspase 3 assay. |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Ahn S, Kim J, Hara MR, Ren XR, Lefkowitz RJ |
284:8855-65 |
7207
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
angiotensin II
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
antiapoptotic |
β-arrestin2 mediates anti-apoptotic signaling through regulation of BAD phosphorylation. |
β-arrestin 2 siRNA treated cells fail to reverse the apoptotic stimuli induced mitochondrial fragmentation. |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Ahn S, Kim J, Hara MR, Ren XR, Lefkowitz RJ |
284:8855-65 |
226081
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
[Sar1,Ile4,Ile8]angiotensin II
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
antiapoptotic |
β-arrestin2 mediates anti-apoptotic signaling through regulation of BAD phosphorylation. |
significant decrease in the levels of cleaved caspase-3 upon apoptotic stimuli treatment |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Ahn S, Kim J, Hara MR, Ren XR, Lefkowitz RJ |
284:8855-65 |
226081
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
[Sar1,Ile4,Ile8]angiotensin II
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
antiapoptotic |
β-arrestin2 mediates anti-apoptotic signaling through regulation of BAD phosphorylation. |
significant decrease in DNA fragmentation |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Ahn S, Kim J, Hara MR, Ren XR, Lefkowitz RJ |
284:8855-65 |
7207
|
A |
Angiotensin receptors |
AGTRA |
AT1 |
Rat |
angiotensin II
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
antiapoptotic |
β-arrestin2 mediates anti-apoptotic signaling through regulation of BAD phosphorylation. |
activation of ribosomal S6 kinase (RSK) which phosphorylates BAD |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Ahn S, Kim J, Hara MR, Ren XR, Lefkowitz RJ |
284:8855-65 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
g protein |
|
Heart disease |
vasoconstrction |
Biased ligand demonstrated cardiac unloading actions while preserving renal function in normal and heart failure canines. |
Biased ligand towards β-arrestin antagonized vasoconstriction. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
g protein |
|
Heart disease |
antidiuresis |
Biased ligand demonstrated cardiac unloading actions while preserving renal function in normal and heart failure canines. |
Biased ligand towards β-arrestin antagonized decrease of glomerular filtration. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
g protein |
|
Heart disease |
antidiuresis |
Biased ligand demonstrated cardiac unloading actions while preserving renal function in normal and heart failure canines. |
Biased ligand towards β-arrestin antagonized increase in sodium reabsorption. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
vasodilatation |
Biased ligand demonstrated cardiac unloading actions while preserving renal function in normal and heart failure canines. |
Biased ligand towards β-arrestin showed balanced vasodilatation. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
increase of cardiac performance |
Biased ligand demonstrated cardiac unloading actions while preserving renal function in normal and heart failure canines. |
Biased ligand towards β-arrestin increased cardiac performance. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
diuresis |
Biased ligand demonstrated cardiac unloading actions while preserving renal function in normal and heart failure canines. |
Biased ligand towards β-arrestin increased renal perfusion. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
diuresis |
Biased ligand towards β-arrestin in combination with furosemide preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. |
Biased ligand towards β-arrestin in combination with furosemide increased urine flow in postinfusion clearance. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
natriuresis |
Biased ligand towards β-arrestin in combination with furosemide preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. |
Biased ligand towards β-arrestin in combination with furosemide increased urinary sodium excretion in postinfusion clearance. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
vasodilatation |
Biased ligand towards β-arrestin in combination with furosemide preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. |
Biased ligand towards β-arrestin in combination with furosemide decreased arterial pressure. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
vasodilatation |
Biased ligand towards β-arrestin in combination with furosemide preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. |
Biased ligand towards β-arrestin in combination with furosemide decreased systemic and pulmonary vascular resistance. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
cardiac unloading |
Biased ligand towards β-arrestin in combination with furosemide preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. |
Biased ligand towards β-arrestin in combination with furosemide decreased atrial natriuretic peptide. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
decreased pressure in left atrium |
Biased ligand towards β-arrestin in combination with furosemide preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. |
Biased ligand towards β-arrestin in combination with furosemide decreased pulmonary capillary wedge pressure. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC Jr |
4:770-8 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
β-arrestin signaling of the D2 class mediates dopaminergic-associated behavior. |
β-arrestin2-knock out mice showed less locomotor activation than in wt mice. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG |
122:261-73 |
|
A |
Dopamine receptors |
DRD3 |
D3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
β-arrestin signaling of the D2 class mediates dopaminergic-associated behavior. |
β-arrestin2-knock out mice showed less locomotor activation than in wt mice. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG |
122:261-73 |
|
A |
Dopamine receptors |
DRD4 |
D4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
β-arrestin signaling of the D2 class mediates dopaminergic-associated behavior. |
β-arrestin2-knock out mice showed less locomotor activation than in wt mice. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG |
122:261-73 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
β-arrestin signaling of the D2 class mediates dopaminergic-associated behavior. |
β-arrestin2-knock out mice showed less vertical climbing activity than in wt mice. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG |
122:261-73 |
|
A |
Dopamine receptors |
DRD3 |
D3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
β-arrestin signaling of the D2 class mediates dopaminergic-associated behavior. |
β-arrestin2-knock out mice showed less vertical climbing activity than in wt mice. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG |
122:261-73 |
|
A |
Dopamine receptors |
DRD4 |
D4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
β-arrestin signaling of the D2 class mediates dopaminergic-associated behavior. |
β-arrestin2-knock out mice showed less vertical climbing activity than in wt mice. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG |
122:261-73 |
10713
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
UNC9975
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
antipsychotic |
β-arrestin2 signaling and recruitment can be a significant contributor to antipsychotic efficacy and protective against motoric side effects. |
Biased ligand induced dose-dependent inhibition of D-amphetamine-induced hyperlocomotion. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL, Jin J |
108:18488-93 |
10713
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
UNC9975
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
antipsychotic |
β-arrestin2 signaling and recruitment can be a significant contributor to antipsychotic efficacy and protective against motoric side effects. |
Biased ligand showed inhibition of PCP-induced hyperlocomotion in wild type-mice which was attenuated in knock out mice. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL, Jin J |
108:18488-93 |
10714
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
UNC9994
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
antipsychotic |
β-arrestin2 signaling and recruitment can be a significant contributor to antipsychotic efficacy and protective against motoric side effects. |
Biased ligand showed inhibition of PCP-induced hyperlocomotion in wild type-mice which was attenuated in knock out mice. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL, Jin J |
108:18488-93 |
10713
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
UNC9975
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
protection against motoric side effects |
β-arrestin2 signaling and recruitment can be a significant contributor to antipsychotic efficacy and protective against motoric side effects. |
Biased ligand showed induction of catalepsy in β-arrestin2-knock out mice but not in wild type mice. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL, Jin J |
108:18488-93 |
10712
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
UNC0006
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
protection against motoric side effects |
β-arrestin2 signaling and recruitment can be a significant contributor to antipsychotic efficacy and protective against motoric side effects. |
Biased ligand showed induction of catalepsy in β-arrestin2-knock out mice but not in wild type mice. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL, Jin J |
108:18488-93 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
β-arrestin-biased receptor caused a significant potentiation of amphetamine-induced lovomotion. |
β-arrestin-biased receptor caused a significant potentiation of amphetamine-induced lovomotion. |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Peterson SM, Pack TF, Wilkins AD, Urs NM, Urban DJ, Bass CE, Lichtarge O, Caron MG |
112:7097-102 |
10714
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
UNC9994
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
antipsychotic |
The antipsychotic like effects of β-arrestin2-biased D2R ligand are driven through striatal antagonism and cortical agonism of D2R-β-arrestin2 signaling. |
Biased ligand showed inhibition of PCP-induced hyperlocomotion in the prefrontal cortex. |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Urs NM, Gee SM, Pack TF, McCorvy JD, Evron T, Snyder JC, Yang X, Rodriguiz RM, Borrelli E, Wetsel WC, Jin J, Roth BL, O'Donnell P, Caron MG |
113:E8178-E8186 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
The antipsychotic like effects of β-arrestin2-biased D2R ligand are driven through striatal antagonism and cortical agonism of D2R-β-arrestin2 signaling. |
Reduced locomotor response in striatal β-arrestin2 deficient mice. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Urs NM, Gee SM, Pack TF, McCorvy JD, Evron T, Snyder JC, Yang X, Rodriguiz RM, Borrelli E, Wetsel WC, Jin J, Roth BL, O'Donnell P, Caron MG |
113:E8178-E8186 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
antipsychotic |
The antipsychotic like effects of β-arrestin2-biased D2R ligand are driven through striatal antagonism and cortical agonism of D2R-β-arrestin2 signaling. |
Loss of antipsychotic-like activity to PCP in mice lacking β-arrestin2 in all D2R neurons but not in striatal D2R neurons. |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Urs NM, Gee SM, Pack TF, McCorvy JD, Evron T, Snyder JC, Yang X, Rodriguiz RM, Borrelli E, Wetsel WC, Jin J, Roth BL, O'Donnell P, Caron MG |
113:E8178-E8186 |
10714
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
UNC9994
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
antipsychotic |
The antipsychotic like effects of β-arrestin2-biased D2R ligand are driven through striatal antagonism and cortical agonism of D2R-β-arrestin2 signaling. |
Biased ligand showed increase of fast spiking interneuron excitability which might elicit antipsychotic activity. |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Urs NM, Gee SM, Pack TF, McCorvy JD, Evron T, Snyder JC, Yang X, Rodriguiz RM, Borrelli E, Wetsel WC, Jin J, Roth BL, O'Donnell P, Caron MG |
113:E8178-E8186 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
partial restoration of locomotion after D2R knock out |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
gi/o-family |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
partial restoration of locomotion after D2R knock out |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
gi/o-family |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
complete restoration of nestlet shredding behavior after D2R knock out |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
partial restoration of locomotion compared to D2R knock out and wild type |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
gi/o-family |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
partial restoration of locomotion compared to D2R knock out and wild type |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
restoration of locomotion compared to D2R knock out and wild type |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
gi/o-family |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
restoration of locomotion compared to D2R knock out and wild type |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Psychiatric disorder |
dopamine-associated behavior |
D2R-driven behavior, nestlet shredding, is driven by D2R/G-protein signaling. D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/β-arrestin signaling. |
potentiated restoration of locomotion compared to D2R knock out and wild type |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Rose SJ, Pack TF, Peterson SM, Payne K, Borrelli E, Caron MG |
43:1164-1173 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
β-arrestin |
|
Psychiatric disorder |
dopamine-associated behavior |
Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation. |
D2R wild type and arrestin biased D2R mice exhibited a robust increase in locomotor activity when treted with cocaine. |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Donthamsetti P, Gallo EF, Buck DC, Stahl EL, Zhu Y, Lane JR, Bohn LM, Neve KA, Kellendonk C, Javitch JA |
25:2086-2100 |
|
A |
Dopamine receptors |
DRD2 |
D2 |
Mouse |
-
|
gi/o-family |
|
Psychiatric disorder |
motivation |
Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation. |
Incentive motivation was enhanced by the upregulation of the wild type D2R but not by the arrestin biased D2R. |
Knock in - mutant receptor with impared signalling |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Donthamsetti P, Gallo EF, Buck DC, Stahl EL, Zhu Y, Lane JR, Bohn LM, Neve KA, Kellendonk C, Javitch JA |
25:2086-2100 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
cardioprotection |
Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity |
significant deterioration in cardiac function |
Knock in - mutant receptor with impared signalling |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
cardioprotection |
Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity |
marked LV dilatation |
Knock in - mutant receptor with impared signalling |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
cardioprotection |
Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity |
reduced fractional shortening |
Knock in - mutant receptor with impared signalling |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
cardioprotection |
Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity |
increased interstitial fibrosis |
Knock in - mutant receptor with impared signalling |
Animals |
Histological examination |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
8872
|
A |
Adrenoceptors |
ADRB1 |
β1-adrenoceptor |
Mouse |
isoprenaline
|
β-arrestin |
|
Heart disease |
cardioprotection |
Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity |
increased apoptotic nuclei |
Knock in - mutant receptor with impared signalling |
Animals |
Histological examination |
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA |
117:2445-58 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
g protein |
|
Analgesia/pain |
opioid related adverse effects |
TRV130 may offer analgesia withreduced risk of opioid‐induced nausea and vomitingcompared to current opioid analgesics |
analgesia with reduced risk of opioid-induced nausea and vomiting |
Biased ligand (towards sig. prot.) |
Humans |
Open-ended questions (report of AEs) |
Soergel DG, Subach RA, Sadler B, Connell J, Marion AS, Cowan CL, Violin JD, Lark MW |
54:351-7 |
226082
|
C |
Metabotropic glutamate receptors |
GRM7 |
mGlu7 |
Rat |
AMN082
|
β-arrestin-2 (non-visual arrestin-3) |
|
Nervous system disease |
neuronal protection |
β-Arr2-dependent Phospho-ERK1/2 reduces sevoflurane neurotoxicity |
relief of developmental sevoflurane-induced neuronal apoptosis |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Wang WY, Wu XM, Jia LJ, Zhang HH, Cai F, Mao H, Xu WC, Chen L, Zhang J, Hu SF |
313:199-212 |
226082
|
C |
Metabotropic glutamate receptors |
GRM7 |
mGlu7 |
Rat |
AMN082
|
β-arrestin-1 (non-visual arrestin-2) |
|
Nervous system disease |
neuronal protection |
Neuronal protection may be mediated by β-arr1-dependent epigenetic modulations |
neuronal protection |
Gene silencing (siRNA) of sig. prot. |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Wang WY, Wu XM, Jia LJ, Zhang HH, Cai F, Mao H, Xu WC, Chen L, Zhang J, Hu SF |
313:199-212 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Human |
TRV027
|
β-arrestin-2 (non-visual arrestin-3) |
|
Heart disease |
decrease in blood pressure |
TRV027 result in rapid and reversible decrease in blood pressure |
significant decrease in mean arterial pressure and diastolic blood pressure |
Biased ligand (towards sig. prot.) |
Humans |
Physical examination |
Soergel DG, Subach RA, Cowan CL, Violin JD, Lark MW |
53:892-9 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Vascular disease |
diuresis |
TRV120027 preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload |
increased urine flow in postinfusion clearance |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Soergel DG, Violin JD, Lark MW, Burnett JC Jr |
5:627-34 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Vascular disease |
natriuresis |
TRV120027 preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload |
increased urinary sodium excretion in postinfusion clearance |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Soergel DG, Violin JD, Lark MW, Burnett JC Jr |
5:627-34 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Vascular disease |
vasodilatation |
TRV120027 preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload |
decreased arterial pressure |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Soergel DG, Violin JD, Lark MW, Burnett JC Jr |
5:627-34 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Vascular disease |
vasodilatation |
TRV120027 preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload |
decreased systemic and pulmonary vascular resistance |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Soergel DG, Violin JD, Lark MW, Burnett JC Jr |
5:627-34 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
cardiac unloading |
TRV120027 preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload |
decreased atrial natriuretic peptide |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Soergel DG, Violin JD, Lark MW, Burnett JC Jr |
5:627-34 |
10649
|
A |
Angiotensin receptors |
AGTR1 |
AT1 |
Dog |
TRV027
|
β-arrestin |
|
Heart disease |
decreased pressure in left atrium |
TRV120027 preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload |
decreased pulmonary capillary wedge pressure |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Boerrigter G, Soergel DG, Violin JD, Lark MW, Burnett JC Jr |
5:627-34 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
atherosclerosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
less atherosclerosis in β-arrestin2-deficient mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
prevention hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
attenuation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
hyperplasia |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
exacerbation of neointimal hyperplasia |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
antiproliferative |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented medial small muscle cell proliferation in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced medial small muscle cell proliferation in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
Vascular disease |
apoptosis |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
reduced small muscle cell apoptosis in β-arrestin1-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR2 |
PAR2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Vascular disease |
antiapoptotic effect |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
augmented small muscle cell apoptosis in β-arrestin2-knock out mice |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
9134
|
A |
Lysophospholipid (LPA) receptors |
LPAR1 |
LPA1 |
Mouse |
LPA
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
9134
|
A |
Lysophospholipid (LPA) receptors |
LPAR2 |
LPA2 |
Mouse |
LPA
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR1 |
PAR1 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR3 |
PAR3 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
|
A |
Proteinase-activated receptors |
PAR4 |
PAR4 |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR1 |
S1P1 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR2 |
S1P2 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR3 |
S1P3 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR4 |
S1P4 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-1 (non-visual arrestin-2) |
|
cardiovascular |
attenuation of proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
increased thymidine incorporation in β-arrestin1-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
10421
|
A |
Lysophospholipid (S1P) receptors |
S1PR5 |
S1P5 |
Mouse |
sphingosine 1-phosphate
|
β-arrestin-2 (non-visual arrestin-3) |
|
cardiovascular |
proliferation |
β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. |
decreased thymidine incorporation in β-arrestin2-knock out cells |
Knock out of sig. prot. |
Animals |
Histological examination |
Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ |
103:70-9 |
9231
|
A |
Ghrelin receptors |
GHSR |
ghrelin |
Mouse |
macimorelin
|
β-arrestin |
|
Nervous system disease |
anticonvulsive |
Possible involvement of β-arrestin signaling mediated by ghrelin-R modulation in the anticonvulsive effects JMV-1843. |
attenuation of seizure severity and decrease in the number of seizures in mice treated with full agonist; effects were abolished in mice treated with a biased G protein agonist |
Biased ligand (towards sig. prot.) |
Animals |
observation of behavior and EEG |
Buckinx A, Van Den Herrewegen Y, Pierre A, Cottone E, Ben Haj Salah K, Fehrentz JA, Kooijman R, De Bundel D, Smolders I |
20 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
g protein |
|
Analgesia/pain |
antinociception/analgesia |
PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties |
antinociception with supraspinal and spinal component |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zador F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R |
176:4434-4445 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
β-arrestin |
|
Analgesia/pain |
rewarding effects and reinforcement |
PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties |
the ligand does not induce conditioned place preference |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zador F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R |
176:4434-4445 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Rat |
PZM21
|
β-arrestin |
|
Analgesia/pain |
rewarding effects and reinforcement |
PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties |
the ligand did not induce drug seeking behavior after abstinence period and no readily self-administration |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zador F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R |
176:4434-4445 |
9942
|
A |
Opioid receptors |
OPRK |
κ |
Mouse |
probe 1.1 [PMID: 24187130]
|
gi/o-family |
|
Analgesia/pain |
antinociception/analgesia |
Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria |
antinociception |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM |
9:ra117 |
9942
|
A |
Opioid receptors |
OPRK |
κ |
Mouse |
probe 1.1 [PMID: 24187130]
|
g protein |
|
Analgesia/pain |
antipruritic |
Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria |
suppression of scratching behaviors |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM |
9:ra117 |
9942
|
A |
Opioid receptors |
OPRK |
κ |
Mouse |
probe 1.1 [PMID: 24187130]
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
sedation |
Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria |
no suppression of ambulation compared to other agonists |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM |
9:ra117 |
9942
|
A |
Opioid receptors |
OPRK |
κ |
Mouse |
probe 1.1 [PMID: 24187130]
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
sedation |
Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria |
no decrease in dopaminergic transmission |
Biased ligand (towards sig. prot.) |
Animals |
measurement of electrophysiology |
Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM |
9:ra117 |
9942
|
A |
Opioid receptors |
OPRK |
κ |
Mouse |
probe 1.1 [PMID: 24187130]
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
sedation |
Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria |
no decrease in dopaminergic transmission |
Biased ligand (towards sig. prot.) |
Animals |
instrument based examination of living organism |
Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM |
9:ra117 |
9942
|
A |
Opioid receptors |
OPRK |
κ |
Rat |
probe 1.1 [PMID: 24187130]
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
dysphoria |
Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria |
the ligand did not alter intracranial self-stimulation when compared to baseline or vehicle |
Biased ligand (towards sig. prot.) |
Animals |
instrument based examination of living organism |
Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM |
9:ra117 |
9942
|
A |
Opioid receptors |
OPRK |
κ |
Rat |
probe 1.1 [PMID: 24187130]
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
dysphoria |
Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria |
administration of the ligand suppressed the effect of lactic acid compared to vehicle administration |
Biased ligand (towards sig. prot.) |
Animals |
instrument based examination of living organism |
Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM |
9:ra117 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
respiratory suppression |
Direct correlation of increasing bias factor with an improved separation of therapeutic benefit from respiratory side effects |
less respiratory suppression in G protein biased ligands |
Biased ligand (towards sig. prot.) |
Animals |
Physical examination |
Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, Cameron MD, Bannister TD, Bohn LM |
171:1165-1175.e13 |
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
-
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
respiratory suppression |
Direct correlation of increasing bias factor with an improved separation of therapeutic benefit from respiratory side effects |
robust respiratory suppression at lower doses of β-arrestin2-biased ligands |
Biased ligand (towards sig. prot.) |
Animals |
Physical examination |
Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, Cameron MD, Bannister TD, Bohn LM |
171:1165-1175.e13 |
9372
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
morphine
|
gi/o-family |
|
Analgesia/pain |
antinociception/analgesia |
Inhibition of β-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine |
analgesia was prolonged and potentiated in β-arrestin 2 knock out mice |
Knock out of sig. prot. |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT |
286:2495-8 |
177523
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
CHEMBL4452384
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
tolerance |
SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented |
SR-17080 showed no tolerance development at 24 mg/kg/day and slight decrease in potency at 48mg/kg/day in male mice; no tolerance development in female mice |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM |
45:416-425 |
177523
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
CHEMBL4452384
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
desensitization |
SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented |
G protein signaling was intact in SR-17018 treated mice in contrary to morphine treated mice |
Biased ligand (towards sig. prot.) |
Animals |
Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) |
Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM |
45:416-425 |
177523
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
CHEMBL4452384
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
tolerance |
SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented |
restoration of morphine tolerance after three days of ligand treatment, which was also established with vehicle treatment |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM |
45:416-425 |
177523
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
CHEMBL4452384
|
g protein |
|
Analgesia/pain |
resensitization |
SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented |
restoration of morphine tolerance after three days of ligand treatment, which was also established with vehicle treatment |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM |
45:416-425 |
177523
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
CHEMBL4452384
|
g protein |
|
Analgesia/pain |
prevention of withdrawal |
SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented |
reduction of withdrawal signs under SR-17018 treatment, similar to buprenorphine |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM |
45:416-425 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
gi/o-family |
|
Analgesia/pain |
antinociception/analgesia |
TRV130 may provide effective, rapid analgesia with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine |
TRV130 produced statistically significant reduction in pain relative to placebo over 24 hours that was similar to that of morphine; analgesia occurred more rapidly with TRV130 at 5- and 30-minute time points |
Biased ligand (towards sig. prot.) |
Humans |
Numeric rating scales (pain intensity, etc.) |
Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F |
10:2413-2424 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
β-arrestin |
|
Analgesia/pain |
nausea and emesis |
TRV130 may provide effective, rapid analgesia with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine |
lower percentages of patients treated with TRV130 experienced nausea and vomiting than patients receiving morphine |
Biased ligand (towards sig. prot.) |
Humans |
Physical examination |
Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F |
10:2413-2424 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
β-arrestin |
|
Analgesia/pain |
respiratory suppression |
TRV130 may provide effective, rapid analgesia with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine |
lower percentages of patients treated with TRV130 experienced respiratory effects than patients receiving morphine |
Biased ligand (towards sig. prot.) |
Humans |
Physical examination |
Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F |
10:2413-2424 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
gi/o-family |
|
Analgesia/pain |
antinociception/analgesia |
TRV130 may be associated with a lower incidence of AEs at dosing regimens associated with comparable analgesia. |
Oliceridine 0,35- and 0,5mg demand dose regimens were consistently superior to placebo and equi-analgesic to morphine (1mg) |
Biased ligand (towards sig. prot.) |
Humans |
Numeric rating scales (pain intensity, etc.) |
Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER |
19:715-731 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
β-arrestin |
|
Analgesia/pain |
respiratory suppression |
TRV130 may be associated with a lower incidence of AEs at dosing regimens associated with comparable analgesia. |
Oliceridine 0,35mg regimen showed a favorable safety and tolerability profile regarding respiratory adverse events compared to morphine (gatekeeping statistical approach) |
Biased ligand (towards sig. prot.) |
Humans |
Physical examination |
Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER |
19:715-731 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Human |
OLICERIDINE
|
β-arrestin |
|
Analgesia/pain |
GI dysfunction; constipation |
TRV130 may be associated with a lower incidence of AEs at dosing regimens associated with comparable analgesia. |
Oliceridine 0,35mg regimen showed a favorable safety and tolerability profile regarding gastrointestinal adverse events compared to morphine (gatekeeping statistical approach) |
Biased ligand (towards sig. prot.) |
Humans |
Physical examination |
Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER |
19:715-731 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
gi/o-family |
|
Analgesia/pain |
respiratory suppression |
PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist |
dose-dependent respiratory depression that was maintained over the 60 min period following drug administration |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G |
175:2653-2661 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
gi/o-family |
|
Analgesia/pain |
tolerance |
PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist |
development of tolerance to the antinociceptive effects |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G |
175:2653-2661 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
respiratory suppression |
PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist |
dose-dependent respiratory depression that was maintained over the 60 min period following drug administration |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G |
175:2653-2661 |
10020
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
PZM21
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
tolerance |
PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist |
development of tolerance to the antinociceptive effects |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G |
175:2653-2661 |
9093
|
A |
Opioid receptors |
OPRM |
μ |
Mouse |
levorphanol
|
β-arrestin-2 (non-visual arrestin-3) |
|
Analgesia/pain |
respiratory suppression |
Levorphanol was a G-protein biased agonist at µ opioid receptor splice variants, consistent with diminished respiratory depressant activity, and displayed incomplete cross tolerance to morphine and oxycodone |
Levorphanol decreased respiratory rate, however, the area under the curve was not significantly different from saline treated mice |
Biased ligand (towards sig. prot.) |
Animals |
Physical examination |
Le Rouzic V, Narayan A, Hunkle A, Marrone GF, Lu Z, Majumdar S, Xu J, Pan YX, Pasternak GW |
128:365-373 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Rat |
OLICERIDINE
|
g protein |
|
Analgesia/pain |
antinociception/analgesia |
The G-protein biased mu-opioid agonist, TRV130, produces reinforcing and antinociceptive effects |
ED50 values for oxycodone and TRV130 were not significantly different |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Austin Zamarripa C, Edwards SR, Qureshi HN, Yi JN, Blough BE, Freeman KB |
192:158-162 |
99920
|
A |
Opioid receptors |
OPRM |
μ |
Rat |
OLICERIDINE
|
g protein |
|
Analgesia/pain |
rewarding effects and reinforcement |
The G-protein biased mu-opioid agonist, TRV130, produces reinforcing and antinociceptive effects |
TRV130 and oxycodone showed the same potency as a reinforcer |
Biased ligand (towards sig. prot.) |
Animals |
Observation of animal behavior (HTR, hot plate, tail-flick, etc.) |
Austin Zamarripa C, Edwards SR, Qureshi HN, Yi JN, Blough BE, Freeman KB |
192:158-162 |
145105
|
A |
Adenosine receptors |
AA1R |
A1 |
Human |
CHEMBL3771208
|
gαob |
|
Analgesia/pain |
Analgesia without cardiorespiratory depression |
Selective activation of GαoB by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression. |
BnOCPA had no effect on heart rate, but markedly reduced the bradycardia evoked by adenosine |
Biased ligand (towards sig. prot.) |
Organ/tissue/slice |
Measurements on excised organ/tissue/slice |
Wall MJ, Hill E, Huckstepp R, Barkan K, Deganutti G, Leuenberger M, Preti B, Winfield I, Carvalho S, Suchankova A, Wei H, Safitri D, Huang X, Imlach W, La Mache C, Dean E, Hume C, Hayward S, Oliver J, Zhao FY, Spanswick D, Reynolds CA, Lochner M, Ladds G, Frenguelli BG |
13:4150 |
145105
|
A |
Adenosine receptors |
AA1R |
A1 |
Human |
CHEMBL3771208
|
gαob |
|
Analgesia/pain |
Analgesia without cardiorespiratory depression |
Selective activation of GαoB by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression. |
BnOCPA had no effect on either heart rate or blood pressure |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Wall MJ, Hill E, Huckstepp R, Barkan K, Deganutti G, Leuenberger M, Preti B, Winfield I, Carvalho S, Suchankova A, Wei H, Safitri D, Huang X, Imlach W, La Mache C, Dean E, Hume C, Hayward S, Oliver J, Zhao FY, Spanswick D, Reynolds CA, Lochner M, Ladds G, Frenguelli BG |
13:4150 |
145105
|
A |
Adenosine receptors |
AA1R |
A1 |
Human |
CHEMBL3771208
|
gαob |
|
Analgesia/pain |
Analgesia without cardiorespiratory depression |
Selective activation of GαoB by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression. |
When co-applied with adenosine or CPA, BnOCPA abolished the bradycardia induced by both agonists |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Wall MJ, Hill E, Huckstepp R, Barkan K, Deganutti G, Leuenberger M, Preti B, Winfield I, Carvalho S, Suchankova A, Wei H, Safitri D, Huang X, Imlach W, La Mache C, Dean E, Hume C, Hayward S, Oliver J, Zhao FY, Spanswick D, Reynolds CA, Lochner M, Ladds G, Frenguelli BG |
13:4150 |
145105
|
A |
Adenosine receptors |
AA1R |
A1 |
Human |
CHEMBL3771208
|
gαob |
|
Analgesia/pain |
Analgesia without cardiorespiratory depression |
Selective activation of GαoB by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression. |
BnOCPA had no appreciable effect on respiration but reduced the depression of respiratory frequency and minute ventilation caused by CPA |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Wall MJ, Hill E, Huckstepp R, Barkan K, Deganutti G, Leuenberger M, Preti B, Winfield I, Carvalho S, Suchankova A, Wei H, Safitri D, Huang X, Imlach W, La Mache C, Dean E, Hume C, Hayward S, Oliver J, Zhao FY, Spanswick D, Reynolds CA, Lochner M, Ladds G, Frenguelli BG |
13:4150 |
145105
|
A |
Adenosine receptors |
AA1R |
A1 |
Human |
CHEMBL3771208
|
gαob |
|
Analgesia/pain |
Analgesia without cardiorespiratory depression |
Selective activation of GαoB by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression. |
BnOCPA potently reversed mechanical allodynia in a dose-dependent manner and exhibits powerful analgesic properties. Prior administration of DPCPX prevented this, confirming the importance of A1Rs. |
Biased ligand (towards sig. prot.) |
Animals |
Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) |
Wall MJ, Hill E, Huckstepp R, Barkan K, Deganutti G, Leuenberger M, Preti B, Winfield I, Carvalho S, Suchankova A, Wei H, Safitri D, Huang X, Imlach W, La Mache C, Dean E, Hume C, Hayward S, Oliver J, Zhao FY, Spanswick D, Reynolds CA, Lochner M, Ladds G, Frenguelli BG |
13:4150 |