Home LiteratureArticle Details
PMID: 20431569 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Teaching old receptors new tricks: biasing seven-transmembrane receptors.

Nature reviews. Drug discovery ·Vol. 9 ·No. 5 ·2010-05-00 ·Pages 373-86

Rajagopal S, Rajagopal K, Lefkowitz RJ

Abstract

Seven-transmembrane receptors (7TMRs; also known as G protein-coupled receptors) are the largest class of receptors in the human genome and are common targets for therapeutics. Originally identified as mediators of 7TMR desensitization, beta-arrestins (arrestin 2 and arrestin 3) are now recognized as true adaptor proteins that transduce signals to multiple effector pathways. Signalling that is mediated by beta-arrestins has distinct biochemical and functional consequences from those mediated by G proteins, and several biased ligands and receptors have been identified that preferentially signal through either G protein- or beta-arrestin-mediated pathways. These ligands are not only useful tools for investigating the biochemistry of 7TMR signalling, they also have the potential to be developed into new classes of therapeutics.

MeSH Terms
Animals Arrestins/metabolism Drug Delivery Systems Drug Design Genome, Human Humans Ligands Receptors, G-Protein-Coupled/metabolism Signal Transduction/drug effects beta-Arrestins
Chemicals
Arrestins Ligands Receptors, G-Protein-Coupled arrestin3 beta-Arrestins seven-transmembrane G-protein-coupled receptor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rajagopal Sudarshan
Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina 27710, USA.
Rajagopal Keshava
Lefkowitz Robert J
References (117)
117 references, click to expand
  1. beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor.
    J Biol Chem. 2006 Jan 13;281(2):1261-73 PMID: 16280323
  2. Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis.
    Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2806-11 PMID: 19202075
  3. The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation.
    J Biol Chem. 2003 Feb 21;278(8):6258-67 PMID: 12473660
  4. Beta-arrestin2 functions as a phosphorylation-regulated suppressor of UV-induced NF-kappaB activation.
    EMBO J. 2005 Dec 21;24(24):4237-46 PMID: 16308565
  5. beta-arrestins: traffic cops of cell signaling.
    Curr Opin Cell Biol. 2004 Apr;16(2):162-8 PMID: 15196559
  6. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes.
    Science. 1999 Jan 29;283(5402):655-61 PMID: 9924018
  7. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7.
    J Biol Chem. 2004 May 28;279(22):23214-22 PMID: 15054093
  8. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins.
    Science. 2002 Oct 25;298(5594):834-6 PMID: 12399592
  9. Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2.
    Cell. 2007 May 4;129(3):511-22 PMID: 17482545
  10. Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein).
    Proc Natl Acad Sci U S A. 1987 Dec;84(24):8879-82 PMID: 2827157
  11. Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization.
    Science. 1996 Jan 19;271(5247):363-6 PMID: 8553074
  12. Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology.
    Trends Pharmacol Sci. 2007 Aug;28(8):382-9 PMID: 17629965
  13. Emerging concepts of guanine nucleotide-binding protein-coupled receptor (GPCR) function and implications for high throughput screening.
    Assay Drug Dev Technol. 2007 Jun;5(3):425-51 PMID: 17638542
  14. A beta-arrestin-biased agonist of the parathyroid hormone receptor (PTH1R) promotes bone formation independent of G protein activation.
    Sci Transl Med. 2009 Oct 7;1(1):1ra1 PMID: 20368153
  15. Historical review: a brief history and personal retrospective of seven-transmembrane receptors.
    Trends Pharmacol Sci. 2004 Aug;25(8):413-22 PMID: 15276710
  16. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor.
    J Biol Chem. 1980 Aug 10;255(15):7108-17 PMID: 6248546
  17. An opioid agonist that does not induce mu-opioid receptor--arrestin interactions or receptor internalization.
    Mol Pharmacol. 2007 Feb;71(2):549-57 PMID: 17090705
  18. Enhanced morphine analgesia in mice lacking beta-arrestin 2.
    Science. 1999 Dec 24;286(5449):2495-8 PMID: 10617462
  19. Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus.
    Mol Pharmacol. 1998 Jul;54(1):94-104 PMID: 9658194
  20. Functional specialization of beta-arrestin interactions revealed by proteomic analysis.
    Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12011-6 PMID: 17620599
  21. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?
    Trends Pharmacol Sci. 2007 Aug;28(8):366-73 PMID: 17629958
  22. Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor.
    Nature. 1996 Oct 3;383(6599):447-50 PMID: 8837779
  23. Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.
    Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10782-7 PMID: 12949261
  24. beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha.
    Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8603-7 PMID: 15173580
  25. beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2.
    J Cell Biol. 2000 Mar 20;148(6):1267-81 PMID: 10725339
  26. beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice.
    J Clin Invest. 2009 May;119(5):1312-21 PMID: 19349687
  27. The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration.
    Neuron. 2000 Oct;28(1):129-38 PMID: 11086989
  28. The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy.
    J Theor Biol. 1996 Aug 21;181(4):381-97 PMID: 8949584
  29. Enhanced rewarding properties of morphine, but not cocaine, in beta(arrestin)-2 knock-out mice.
    J Neurosci. 2003 Nov 12;23(32):10265-73 PMID: 14614085
  30. High-content screening of known G protein-coupled receptors by arrestin translocation.
    Methods Enzymol. 2006;414:63-78 PMID: 17110187
  31. beta-Arrestin: a protein that regulates beta-adrenergic receptor function.
    Science. 1990 Jun 22;248(4962):1547-50 PMID: 2163110
  32. Beta-arrestin signaling and regulation of transcription.
    J Cell Sci. 2007 Jan 15;120(Pt 2):213-8 PMID: 17215450
  33. Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor.
    J Biol Chem. 2004 Aug 20;279(34):35518-25 PMID: 15205453
  34. Nuclear beta-arrestin1 functions as a scaffold for the dephosphorylation of STAT1 and moderates the antiviral activity of IFN-gamma.
    Mol Cell. 2008 Sep 5;31(5):695-707 PMID: 18775329
  35. Transduction of receptor signals by beta-arrestins.
    Science. 2005 Apr 22;308(5721):512-7 PMID: 15845844
  36. Simultaneous coupling of alpha 2-adrenergic receptors to two G-proteins with opposing effects. Subtype-selective coupling of alpha 2C10, alpha 2C4, and alpha 2C2 adrenergic receptors to Gi and Gs.
    J Biol Chem. 1992 Aug 5;267(22):15795-801 PMID: 1322406
  37. Beta-arrestin-mediated localization of smoothened to the primary cilium.
    Science. 2008 Jun 27;320(5884):1777-81 PMID: 18497258
  38. alpha-Thrombin induces rapid and sustained Akt phosphorylation by beta-arrestin1-dependent and -independent mechanisms, and only the sustained Akt phosphorylation is essential for G1 phase progression.
    J Biol Chem. 2002 May 24;277(21):18640-8 PMID: 11901145
  39. Beta-arrestin-biased ligands at seven-transmembrane receptors.
    Trends Pharmacol Sci. 2007 Aug;28(8):416-22 PMID: 17644195
  40. Light-dependent phosphorylation of rhodopsin: number of phosphorylation sites.
    Biochemistry. 1982 Jun 8;21(12):3014-22 PMID: 6980670
  41. Value of novelty?
    Nat Rev Drug Discov. 2002 Aug;1(8):571-2 PMID: 12402497
  42. Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated pathway of chemotaxis.
    Mol Pharmacol. 2005 Apr;67(4):1229-36 PMID: 15635042
  43. The genetic design of signaling cascades to record receptor activation.
    Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):64-9 PMID: 18165312
  44. Akt/GSK3 signaling in the action of psychotropic drugs.
    Annu Rev Pharmacol Toxicol. 2009;49:327-47 PMID: 18928402
  45. Regulation of GPCRs by endocytic membrane trafficking and its potential implications.
    Annu Rev Pharmacol Toxicol. 2008;48:537-68 PMID: 18184106
  46. Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection.
    J Clin Invest. 2007 Sep;117(9):2445-58 PMID: 17786238
  47. Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM receptors.
    Trends Pharmacol Sci. 2007 Aug;28(8):407-15 PMID: 17629960
  48. Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation.
    Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14555-60 PMID: 18787115
  49. Discrete activation of transduction pathways associated with acetylcholine m1 receptor by several muscarinic ligands.
    Eur J Pharmacol. 1994 Mar 15;267(1):21-31 PMID: 8206127
  50. Morphine side effects in beta-arrestin 2 knockout mice.
    J Pharmacol Exp Ther. 2005 Sep;314(3):1195-201 PMID: 15917400
  51. A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila.
    Neuron. 2000 Oct;28(1):139-52 PMID: 11086990
  52. Crosstalk between G-protein-coupled receptors and epidermal growth factor receptor in cancer.
    Front Biosci. 2008 Jan 01;13:1857-65 PMID: 17981673
  53. Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands.
    Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9649-54 PMID: 19497875
  54. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior.
    Cell. 2005 Jul 29;122(2):261-73 PMID: 16051150
  55. Independent beta-arrestin2 and Gq/protein kinase Czeta pathways for ERK stimulated by angiotensin type 1A receptors in vascular smooth muscle cells converge on transactivation of the epidermal growth factor receptor.
    J Biol Chem. 2009 May 1;284(18):11953-62 PMID: 19254952
  56. Distinct conformational changes in beta-arrestin report biased agonism at seven-transmembrane receptors.
    Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):9988-93 PMID: 18621717
  57. Bioluminescence resonance energy transfer assays reveal ligand-specific conformational changes within preformed signaling complexes containing delta-opioid receptors and heterotrimeric G proteins.
    J Biol Chem. 2008 May 30;283(22):15078-88 PMID: 18381293
  58. The BRET2/arrestin assay in stable recombinant cells: a platform to screen for compounds that interact with G protein-coupled receptors (GPCRS).
    J Recept Signal Transduct Res. 2002 Feb-Nov;22(1-4):533-41 PMID: 12503639
  59. Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments.
    Proc Natl Acad Sci U S A. 1986 Mar;83(5):1174-8 PMID: 3006038
  60. Beta-arrestin is a necessary component of Wnt/beta-catenin signaling in vitro and in vivo.
    Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6690-5 PMID: 17426148
  61. Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo.
    Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1079-84 PMID: 18195357
  62. Structure and function of the third intracellular loop of the 5-hydroxytryptamine2A receptor: the third intracellular loop is alpha-helical and binds purified arrestins.
    J Neurochem. 1999 May;72(5):2206-14 PMID: 10217304
  63. GPCR functional selectivity has therapeutic impact.
    Trends Pharmacol Sci. 2007 Aug;28(8):390-6 PMID: 17629962
  64. CXCR4 dimerization and beta-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome.
    Blood. 2008 Jul 1;112(1):34-44 PMID: 18436740
  65. Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes.
    Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16284-9 PMID: 17060617
  66. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery.
    Assay Drug Dev Technol. 2007 Feb;5(1):137-44 PMID: 17355206
  67. Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy.
    Mol Pharmacol. 2006 Nov;70(5):1575-84 PMID: 16901982
  68. Role of beta-arrestin 1 in the metastatic progression of colorectal cancer.
    Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1492-7 PMID: 16432186
  69. beta -Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport.
    J Biol Chem. 2001 Nov 23;276(47):43663-7 PMID: 11546805
  70. beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation.
    J Biol Chem. 2005 Mar 4;280(9):8041-50 PMID: 15611106
  71. Nicotinic acid: an old drug with a promising future.
    Br J Pharmacol. 2008 Mar;153 Suppl 1:S68-75 PMID: 18037924
  72. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation.
    J Biol Chem. 2006 Apr 21;281(16):10856-64 PMID: 16492667
  73. Cardiac-specific overexpression of AT1 receptor mutant lacking G alpha q/G alpha i coupling causes hypertrophy and bradycardia in transgenic mice.
    J Clin Invest. 2005 Nov;115(11):3045-56 PMID: 16276415
  74. beta-Adrenergic receptor kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation.
    J Biol Chem. 1988 Mar 15;263(8):3893-7 PMID: 2831211
  75. Agonist-receptor efficacy. II. Agonist trafficking of receptor signals.
    Trends Pharmacol Sci. 1995 Jul;16(7):232-8 PMID: 7667897
  76. G protein-independent cell-based assays for drug discovery on seven-transmembrane receptors.
    Biotechnol Annu Rev. 2008;14:253-74 PMID: 18606367
  77. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta -arrestin-dependent scaffolding complex.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11086-91 PMID: 10995467
  78. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription.
    Cell. 2005 Dec 2;123(5):833-47 PMID: 16325578
  79. 3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice.
    J Med Chem. 2008 Aug 28;51(16):5101-8 PMID: 18665582
  80. Novel function of beta-arrestin2 in the nucleus of mature spermatozoa.
    J Cell Sci. 2006 Aug 1;119(Pt 15):3047-56 PMID: 16820410
  81. A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model.
    J Biol Chem. 1993 Mar 5;268(7):4625-36 PMID: 8095262
  82. Pharmacological characterization of the D2 dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary.
    Mol Pharmacol. 1983 May;23(3):576-84 PMID: 6306429
  83. Arrestins block G protein-coupled receptor-mediated apoptosis.
    J Biol Chem. 2004 Jun 4;279(23):24578-84 PMID: 15051714
  84. Side-chain substitutions within angiotensin II reveal different requirements for signaling, internalization, and phosphorylation of type 1A angiotensin receptors.
    Mol Pharmacol. 2002 Apr;61(4):768-77 PMID: 11901215
  85. Monitoring agonist-promoted conformational changes of beta-arrestin in living cells by intramolecular BRET.
    EMBO Rep. 2005 Apr;6(4):334-40 PMID: 15776020
  86. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12.
    Blood. 2005 Mar 15;105(6):2449-57 PMID: 15536153
  87. Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol.
    J Clin Invest. 2007 Jan;117(1):229-35 PMID: 17200720
  88. Beta-adrenergic receptor kinase: primary structure delineates a multigene family.
    Science. 1989 Oct 13;246(4927):235-40 PMID: 2552582
  89. Selective signaling via unique M1 muscarinic agonists.
    Ann N Y Acad Sci. 1993 Sep 24;695:300-3 PMID: 8239299
  90. Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance.
    Nature. 2009 Feb 26;457(7233):1146-9 PMID: 19122674
  91. beta-arrestin-biased agonism at the beta2-adrenergic receptor.
    J Biol Chem. 2008 Feb 29;283(9):5669-76 PMID: 18086673
  92. Measurement of the millisecond activation switch of G protein-coupled receptors in living cells.
    Nat Biotechnol. 2003 Jul;21(7):807-12 PMID: 12808462
  93. Desensitization of G protein-coupled receptors and neuronal functions.
    Annu Rev Neurosci. 2004;27:107-44 PMID: 15217328
  94. beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation.
    J Biol Chem. 2002 Mar 15;277(11):9429-36 PMID: 11777902
  95. Beta-arrestins and cell signaling.
    Annu Rev Physiol. 2007;69:483-510 PMID: 17305471
  96. Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis.
    J Biol Chem. 2003 Dec 19;278(51):51334-9 PMID: 14534298
  97. Cell-based assays in GPCR drug discovery.
    Biotechnol J. 2008 Apr;3(4):471-83 PMID: 18383022
  98. A beta-arrestin 2 signaling complex mediates lithium action on behavior.
    Cell. 2008 Jan 11;132(1):125-36 PMID: 18191226
  99. Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.
    J Pharmacol Exp Ther. 2007 Jun;321(3):1054-61 PMID: 17337633
  100. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds.
    Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2449-54 PMID: 11226259
  101. The role of a conserved region of the second intracellular loop in AT1 angiotensin receptor activation and signaling.
    Endocrinology. 2003 Jun;144(6):2220-8 PMID: 12746278
  102. Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways.
    Mol Cell. 2004 May 7;14(3):303-17 PMID: 15125834
  103. Agonist-receptor-arrestin, an alternative ternary complex with high agonist affinity.
    J Biol Chem. 1997 Nov 14;272(46):28849-52 PMID: 9360951
  104. {beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD Phosphorylation.
    J Biol Chem. 2009 Mar 27;284(13):8855-65 PMID: 19171933
  105. Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation.
    J Biol Chem. 2005 Mar 11;280(10):9528-35 PMID: 15634674
  106. Light-dependent phosphorylation of rhodopsin. Purification and properties of rhodopsin kinase.
    J Biol Chem. 1978 Oct 10;253(19):7040-6 PMID: 690139
  107. Molecular basis of inverse agonism in a G protein-coupled receptor.
    Nat Chem Biol. 2005 Jun;1(1):25-8 PMID: 16407989
  108. Beta-arrestin 2 modulates the activity of nuclear receptor RAR beta2 through activation of ERK2 kinase.
    Oncogene. 2006 Jan 12;25(2):218-29 PMID: 16170358
  109. Beta-arrestin-mediated signaling regulates protein synthesis.
    J Biol Chem. 2008 Apr 18;283(16):10611-20 PMID: 18276584
  110. Structural diversity of G protein-coupled receptors and significance for drug discovery.
    Nat Rev Drug Discov. 2008 Apr;7(4):339-57 PMID: 18382464
  111. A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis.
    J Biol Chem. 2003 Sep 5;278(36):34418-26 PMID: 12821670
  112. A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling.
    Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62 PMID: 17925438
  113. Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the beta-adrenergic receptor.
    Proc Natl Acad Sci U S A. 1983 Jun;80(11):3173-7 PMID: 6304694
  114. Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI.
    Nat Immunol. 2000 Sep;1(3):227-33 PMID: 10973280
  115. Profiling of multiple signal pathway activities by multiplexing antibody and GFP-based translocation assays.
    Comb Chem High Throughput Screen. 2008 Aug;11(7):537-44 PMID: 18694390
  116. Imaging CXCR4 signaling with firefly luciferase complementation.
    Anal Chem. 2008 Jul 15;80(14):5565-73 PMID: 18533683
  117. Relative opioid efficacy is determined by the complements of the G protein-coupled receptor desensitization machinery.
    Mol Pharmacol. 2004 Jul;66(1):106-12 PMID: 15213301
Article Info
Journal
Nature reviews. Drug discovery
Abbr.
Nat Rev Drug Discov
ISSN
1474-1784
DOI
10.1038/nrd3024
Published
2010-05-00
Pages
373-86
Language
English
Region
England
NLM ID
101124171
PMCID
PMC2902265
Subset
IM
Grants
NHLBI NIH HHS · T32 HL007101 · United States
NHLBI NIH HHS · R01 HL070631-04 · United States
NHLBI NIH HHS · R01 HL016037 · United States
NHLBI NIH HHS · HL70631 · United States
NHLBI NIH HHS · R01 HL016037-37 · United States
NHLBI NIH HHS · HL16037 · United States
NHLBI NIH HHS · T32 HL007101-34 · United States
NHLBI NIH HHS · HL07101-34 · United States
NHLBI NIH HHS · R01 HL070631 · United States
External Links
PubMed source DOI: 10.1038/nrd3024 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2