GPCRdb

Pathway effects

	Receptor					Ligand	Pathway	Therapeutic area	Pathway effect outcome				Experiment			Reference
	Class	Rec Fam	UniProt	GtP	Species	Name	Effector		Effect type	High level term	Summary	Details	Pathway distinction	System	Method	Authors	DOI
802	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
802	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
802	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
802	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
802	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
370	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
370	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
370	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
370	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
370	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
1453	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
1453	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
1453	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
1453	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
2089	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
1453	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
2089	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
2089	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
2089	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
2089	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
959	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
959	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
959	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
2402	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
2402	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
2402	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
2402	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
2402	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
2402	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
2402	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
171914	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
171914	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
171914	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
802	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
802	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
802	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
370	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
802	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
3185	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
621	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
2089	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
621	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
802	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
802	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
370	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
171784	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
171784	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
171784	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
171784	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
219354	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.)	Resende KA, Zhao R, Liu Y, Barath E, Lercher JA	14:16663
219354	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.)	Resende KA, Zhao R, Liu Y, Barath E, Lercher JA	14:16663
219354	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.)	Resende KA, Zhao R, Liu Y, Barath E, Lercher JA	14:16663
3239	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
3239	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
2579	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
2579	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
2579	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
2579	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
2579	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
1497	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
1497	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
1497	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
1497	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
1497	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
219355	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
219355	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
219355	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
219355	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
219355	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
219355	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
219355	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
219355	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
219355	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
219355	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
219355	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
419	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
219356	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
3875	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
3875	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
3875	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
3875	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
157529	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
417	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
417	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
219357	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
219357	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
219357	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
93143	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
93143	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
93143	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
93143	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
93143	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
93143	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
93143	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
93143	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
93143	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
93143	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
3244	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
3244	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
3244	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
3244	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
93143	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
93143	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
93143	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
93143	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
219358	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
219358	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
219358	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
219358	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
219358	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
219358	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
219358	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
219359	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
419	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
419	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
219360	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
219360	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
419	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3939	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
3939	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
3940	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
3939	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
3938	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
3940	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
3940	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
2089	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
2089	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
2089	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
2089	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
2089	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
93143	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
219361	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
219361	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
3875	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
2353	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
2353	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
3647	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
3647	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
3647	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
3647	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
3647	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
3647	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
3647	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
3647	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
3647	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
3647	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
2451	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
3244	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
3244	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
3244	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
3166	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
3166	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
3166	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
3166	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
3166	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
3166	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
3166	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
2592	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
170742	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
170742	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
170742	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
170742	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
170742	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
93143	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
93143	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
93143	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
93143	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
93143	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
93143	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
3244	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
3244	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
3244	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
3244	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
2311	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
93143	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
93143	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
138325	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
138325	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
138325	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
138325	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
138325	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

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