Opioid receptor interacting proteins and the control of opioid signaling

Current Pharmaceutical Design

Volumn 19, Issue 42, 2013, Pages 7333-7347

  Lamberts, Jennifer T ^a   Traynor, John R ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

Arrestins; Biased agonism; Drug discovery; G protein coupled receptor kinases; Opioid receptors; Protein kinase C; Regulator of G protein signaling proteins

Indexed keywords

ANALGESIC AGENT; G PROTEIN COUPLED RECEPTOR KINASE; OPIATE; OPIATE RECEPTOR; PROTEIN KINASE C; RETINA S ANTIGEN; RGS PROTEIN;

DRUG DESIGN; DRUG TARGETING; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW;

ANIMALS; HUMANS; OPIOID PEPTIDES; RECEPTORS, OPIOID; RGS PROTEINS; SIGNAL TRANSDUCTION;

EID: 84891846847     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161281942140105160625     Document Type: Review

References (220)

1. Kieffer BL, Evans CJ. Opioid receptors: From binding sites to visible molecules in vivo. Neuropharmacology 2009; 56: 205-12
2. Dhawan BN, Cesselin F, Raghubir R, et al. International union of pharmacology. XII. Classification of opioid receptors. J Pharmacol Exp Ther 1996; 48: 567-92.
3. Kieffer BL. Opioids: First lessons from knockout mice. Trends Pharmacol Sci 1999; 20: 19-26.
4. Pert CB, Snyder SH. Opiate receptor: Demonstration in nervous tissue. Science 1973; 179: 1011-4.
5. 3H) etorphine to rat-brain homogenate. Proc Natl Acad Sci USA 1973; 70: 1947-9.
6. Terenius L. Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. Acta Pharmacol Toxicol (Copenh) 1973; 32: 317-20.
7. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE. The effects of morphineand nalorphinelike drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 1976; 197: 517-32.
8. Lord JA, Waterfield AA, Hughes J, Kosterlitz HW. Endogenous opioid peptides: Multiple agonists and receptors. Nature 1977; 267: 495-9.
9. Evans CJ, Keith DE, Morrison H, Magendzo K, Edwards RH. Cloning of a delta opioid receptor by functional expression. Science 1992; 258: 1952-5.
10. Kieffer BL, Befort K, Gaveriaux-Ruff C, Hirth CG. The deltaopioid receptor: Isolation of a cDNA by expression cloning and pharmacological characterization. Proc Natl Acad Sci USA 1992; 89: 12048-52.
11. Kieffer BL. Recent advances in molecular recognition and signal transduction of active peptides: Receptors for opioid peptides. Cell Mol Neurobiol 1995; 15: 615-35.
12. Reisine T, Bell GI. Molecular biology of opioid receptors. Trends Neurosci 1993; 16: 506-10.
13. Satoh M, Minami M. Molecular pharmacology of the opioid receptors. Pharmacol Ther 1995; 68: 343-64.
14. Mogil JS, Pasternak GW. The molecular and behavioral pharmacology of the orphanin FQ/nociceptin peptide and receptor family. Pharmacol Rev 2001; 53: 381-415.
15. Al-Hasani R, Bruchas MR. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 2011; 115: 1363-81.
16. Martin M, Matifas A, Maldonado R, Kieffer BL. Acute antinociceptive responses in single and combinatorial opioid receptor knockout mice: Distinct mu, delta and kappa tones. Eur J Neurosci 2003; 17: 701-8.
17. Matthes HW, Maldonado R, Simonin F, et al. Loss of morphineinduced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature 1996; 383: 819-23.
18. Simonin F, Valverde O, Smadja C, et al. Disruption of the-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective-agonist U-50,488H and attenuates morphine withdrawal. EMBO J 1998; 17: 886-97.
19. Broom DC, Nitsche JF, Pintar JE, Rice KC, Woods JH, Traynor JR. Comparison of receptor mechanisms and efficacy requirements for-agonist-induced convulsive activity and antinociception in mice. J Pharmacol Exp Ther 2002; 303: 723-9.
20. Filliol D, Ghozland S, Chluba J, et al. Mice deficient forandopioid receptors exhibit opposing alterations of emotional responses. Nat Genet 2000; 25: 195-200.
21. Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem 1987; 56: 615-49.
22. Milligan G, Kostenis E. Heterotrimeric G-proteins: A short history. Br J Pharmacol 2006; 147 Suppl S46-55.
23. Chung KY, Rasmussen SG, Liu T, et al. Conformational changes in the G protein Gs induced by the 2 adrenergic receptor. Nature 2011; 477: 611-5.
24. Westfield GH, Rasmussen SG, Su M, et al. Structural flexibility of the G s alpha-helical domain in the 2-adrenoceptor Gs complex. Proc Natl Acad Sci USA 2011; 108: 16086-91.
25. Wettschureck N, Offermanns S. Mammalian G proteins and their cell type specific functions. Physiol Rev 2005; 85: 1159-204.
26. Laugwitz KL, Offermanns S, Spicher K, Schultz G. Mu and delta opioid receptors differentially couple to G protein subtypes in membranes of human neuroblastoma SH-SY5Y cells. Neuron 1993; 10: 233-42.
27. Prather PL, McGinn TM, Claude Pa, Liu-Chen LY, Loh HH, Law PY. Properties of a-opioid receptor expressed in CHO cells: interaction with multiple G-proteins is not specific for any individual G subunit and is similar to that of other opioid receptors. Brain Res Mol Brain Res 1995; 29: 336-46.
28. Roerig SC, Loh HH, Law PY. Identification of three separate guanine nucleotide-binding proteins that interact with the-opioid receptor in NG108-15 neuroblastoma x glioma hybrid cells. Mol Pharmacol 1992; 41: 822-31.
29. Sharma SK, Klee WA, Nirenberg M. Opiate-dependent modulation of adenylate cyclase. Proc Natl Acad Sci USA 1977; 74: 3365-9.
30. Hescheler J, Rosenthal W, Trautwein W, Schultz G. The GTP-binding protein, Go, regulates neuronal calcium channels. Nature 1987; 325: 445-7.
31. Henry DJ, Grandy DK, Lester HA, Davidson N, Chavkin C. Opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes. Mol Pharmacol 1995; 47: 551-7.
32. North RA, Williams JT, Surprenant A, Christie MJ. M and receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci USA 1987; 84: 5487-91.
33. 2+ from intracellular stores in transfected neuro2a cells by activation of multiple opioid receptor subtypes. Biochem Pharmacol 1997; 54: 809-18.
34. Fukuda K, Kato S, Morikawa H, Shoda T, Mori K. Functional coupling of the-,-, and-opioid receptors to mitogen-activated protein kinase and arachidonate release in Chinese hamster ovary cells. J Neurochem 1996; 67: 1309-16.
35. Law PY, Wong YH, Loh HH. Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol 2000; 40: 389-430.
36. Hollinger S, Hepler JR. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 2002; 54: 527-59.
37. Ross EM, Wilkie TM. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 2000; 69: 795-827.
38. De Vries L, Zheng B, Fischer T, Elenko E, Farquhar MG. The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol 2000; 40: 235-71.
39. Gainetdinov RR, Premont RT, Bohn LM, Lefkowitz RJ, Caron MG. Desensitization of G protein-coupled receptors and neuronal functions. Annu Rev Neurosci 2004; 27: 107-44.
40. Kelly E, Bailey CP, Henderson G. Agonist-selective mechanisms of GPCR desensitization. Br J Pharmacol 2008; 153 Suppl: S379-88.
41. Luttrell LM, Lefkowitz RJ. The role of-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 2002; 115: 455-65.
42. Whistler JL, Enquist J, Marley A, et al. Modulation of postendocytic sorting of G protein-coupled receptors. Science 2002; 297: 615-20.
43. Nagi K, Piñeyro G. Regulation of opioid receptor signalling: Implications for the development of analgesic tolerance. Mol Brain 2011; 4: 25.
44. Shenoy SK, Lefkowitz RJ.-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci 2011; 32: 521-33.
45. Bruchas MR, Chavkin C. Kinase cascades and ligand-directed signaling at the opioid receptor. Psychopharmacology (Berl) 2010; 210: 137-47.
46. Alfaras-Melainis K, Gomes I, Rozenfeld R, Zachariou V, Devi L. Modulation of opioid receptor function by protein-protein interactions. Front Biosci 2009; 14: 3594-607.
47. Milligan G. Opioid receptors and their interacting proteins. Neuromolecular Med 2005; 7: 51-9.
48. Dohlman HG, Song J, Ma D, Courchesne WE, Thorner J. Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: Expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein subunit). Mol Cell Biol 1996; 16: 5194-209.
49. Siderovski DP, Hessel A, Chung S, Mak TW, Tyers M. A new family of regulators of G-protein-coupled receptors? Curr Biol 1996; 6: 211-2.
50. Koelle MR, Horvitz HR. EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins. Cell 1996; 84: 115-25.
51. Tesmer JJ, Berman DM, Gilman AG, Sprang SR. Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Cell 1997; 89: 251-61.
52. Sethakorn N, Yau DM, Dulin NO. Non-canonical functions of RGS proteins. Cell Signal 2010; 22: 1274-81.
53. Traynor J. mu-Opioid receptors and regulators of G protein signaling (RGS) proteins: From a symposium on new concepts in mu-opioid pharmacology. Drug Alcohol Depend 2011; 121: 173-80.
54. DiBello PR, Garrison TR, Apanovitch DM, et al. Selective uncoupling of RGS action by a single point mutation in the G protein alpha-subunit. J Biol Chem 1998; 273: 5780-4.
55. Lan KL, Sarvazyan NA, Taussig R, et al. A point mutation in G o and G i1 blocks interaction with regulator of G protein signaling proteins. J Biol Chem 1998; 273: 12794-7.
56. Clark MJ, Traynor JR. Assays for G-protein-coupled receptor signaling using RGS-insensitive G subunits. Methods Enzymol 2004; 389: 155-69.
57. Fu Y, Zhong H, Nanamori M, et al. RGS-insensitive G-protein mutations to study the role of endogenous RGS proteins. Methods Enzymol 2004; 389: 229-43.
58. Kaur K, Kehrl JM, Charbeneau RA, Neubig RR. RGS-insensitive G subunits: Probes of G subtype-selective signaling and physiological functions of RGS proteins. Methods Mol Biol 2011; 756: 75-98.
59. Clark MJ, Linderman JJ, Traynor JR. Endogenous regulators of G protein signaling differentially modulate full and partial mu-opioid agonists at adenylyl cyclase as predicted by a collision coupling model. Mol Pharmacol 2008; 73: 1538-48.
60. Clark MJ, Harrison C, Zhong H, Neubig RR, Traynor JR. Endogenous RGS protein action modulates mu-opioid signaling through Galphao. Effects on adenylyl cyclase, extracellular signalregulated kinases, and intracellular calcium pathways. J Biol Chem 2003; 278: 9418-25.
61. Clark MJ, Traynor JR. Endogenous regulator of G protein signaling proteins reduce-opioid receptor desensitization and downregulation and adenylyl cyclase tolerance in C6 cells. J Pharmacol Exp Ther 2005; 312: 809-15.
62. Clark MJ, Neubig RR, Traynor JR. Endogenous regulator of G protein signaling proteins suppress G o-dependent,-opioid agonist-mediated adenylyl cyclase supersensitization. J Pharmacol Exp Ther 2004; 310: 215-22.
63. Kimple AJ, Bosch DE, Giguère PM, Siderovski DP. Regulators of G-protein signaling and their G substrates: Promises and challenges in their use as drug discovery targets. Pharmacol Rev 2011; 63: 728-49.
64. Bansal G, Druey KM, Xie Z. R4 RGS proteins: Regulation of Gprotein signaling and beyond. Pharmacol Ther 2007; 116: 473-95.
65. Bernstein LS, Grillo AA, Loranger SS, Linder ME. RGS4 binds to membranes through an amphipathic a-helix. J Biol Chem 2000; 275: 18520-6.
66. Heximer SP, Watson N, Linder ME, Blumer KJ, Hepler JR. RGS2/G0S8 is a selective inhibitor of Gq function. Proc Natl Acad Sci USA 1997; 94: 14389-93.
67. Erdely HA, Lahti RA, Lopez MB, et al. Regional expression of RGS4 mRNA in human brain. Eur J Neurosci 2004; 19: 3125-8.
68. Gold SJ, Ni YG, Dohlman HG, Nestler EJ. Regulators of G-protein signaling (RGS) proteins: Region-specific expression of nine subtypes in rat brain. J Neurosci 1997; 17: 8024-37.
69. Zhang S, Watson N, Zahner J, Rottman JN, Blumer KJ, Muslin AJ. RGS3 and RGS4 are GTPase activating proteins in the heart. J Mol Cell Cardiol 1998; 30: 269-76.
70. Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ. Anatomy of CNS opioid receptors. Trends Neurosci 1988; 11: 308-14.
71. Georgoussi Z, Leontiadis L, Mazarakou G, Merkouris M, Hyde K, Hamm H. Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the muand delta-opioid receptors regulate opioid receptor signaling. Cell Signal 2006; 18: 771-82.
72. Leontiadis LJ, Papakonstantinou MP, Georgoussi Z. Regulator of G protein signaling 4 confers selectivity to specific G proteins to modulate muand delta-opioid receptor signaling. Cell Signal 2009; 21: 1218-28.
73. Garzon J, Rodriguez-Munoz M, Sanchez-Blazquez P. Morphine alters the selective association between-opioid receptors and specific RGS proteins in mouse periaqueductal gray matter. Neuropharmacology 2005; 48: 853-68.
74. Garnier M, Zaratin PF, Ficalora G, et al. Up-regulation of regulator of G protein signaling 4 expression in a model of neuropathic pain and insensitivity to morphine. J Pharmacol Exp Ther 2003; 304: 1299-306.
75. Talbot JN, Roman DL, Clark MJ, et al. Differential modulation of mu-opioid receptor signaling to adenylyl cyclase by regulators of G protein signaling proteins 4 or 8 and 7 in permeabilised C6 cells is G subtype dependent. J Neurochem 2010; 112: 1026-34.
76. Xie Z, Li Z, Guo L, et al. Regulator of G protein signaling proteins differentially modulate signaling of mu and delta opioid receptors. Eur J Pharmacol 2007; 565: 45-53.
77. Gold SJ, Han MH, Herman AE, et al. Regulation of RGS proteins by chronic morphine in rat locus coeruleus. Eur J Neurosci 2003; 17: 971-80.
78. Potenza MN, Gold SJ, Roby-Shemkowitz A, Lerner MR, Nestler EJ. Effects of regulators of G protein-signaling proteins on the functional response of the mu-opioid receptor in a melanophorebased assay. J Pharmacol Exp Ther 1999; 291: 482-91.
79. Wang Q, Liu-Chen L-YY, Traynor JR. Differential modulation ofand-opioid receptor agonists by endogenous RGS4 protein in SH-SY5Y cells. J Biol Chem 2009; 284: 18357-67.
80. Ulens C, Daenens P, Tytgat J. Changes in GIRK1/GIRK2 deactivation kinetics and basal activity in the presence and absence of RGS4. Life Sci 2000; 67: 2305-17.
81. Nakagawa T, Minami M, Satoh M. Up-regulation of RGS4 mRNA by opioid receptor agonists in PC12 cells expressing clonedor-opioid receptors. Eur J Pharmacol 2001; 433: 29-36.
82. Han MH, Renthal W, Ring RH, et al. Brain region specific actions of regulator of G protein signaling 4 oppose morphine reward and dependence but promote analgesia. Biol Psychiatry 2010; 67: 761-9.
83. Garzon J, Rodriguez-Diaz M, Lopez-Fando A, Sanchez-Blazquez P. RGS9 proteins facilitate acute tolerance to mu-opioid effects. Eur J Neurosci 2001; 13: 801-11.
84. Garzon J, Rodriguez-Munoz M, Lopez-Fando A, SanchezBlazquez P. The RGSZ2 protein exists in a complex with muopioid receptors and regulates the desensitizing capacity of Gz proteins. Neuropsychopharmacology 2005; 30: 1632-48.
85. Garzon J, Rodriguez-Munoz M, Lopez-Fando A, Garcia-Espana A, Sanchez-Blazquez P. RGSZ1 and GAIP regulate mubut not deltaopioid receptors in mouse CNS: Role in tachyphylaxis and acute tolerance. Neuropsychopharmacology 2004; 29: 1091-104.
86. Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, Garzón J. RGS-Rz and RGS9-2 proteins control mu-opioid receptor desensitisation in CNS: the role of activated Galphaz subunits. Neuropharmacology 2005; 48: 134-50.
87. Elenko E, Fischer T, Niesman I, et al. Spatial regulation of G i protein signaling in clathrin-coated membrane microdomains containing GAIP. Mol Pharmacol 2003; 64: 11-20.
88. Xie G-X, Yanagisawa Y, Ito E, et al. N-terminally truncated variant of the mouse GAIP/RGS19 lacks selectivity of full-length GAIP/RGS19 protein in regulating ORL1 receptor signaling. J Mol Biol 2005; 353: 1081-92.
89. Anderson GR, Posokhova E, Martemyanov KA. The R7 RGS protein family: Multi-subunit regulators of neuronal G protein signaling. Cell Biochem Biophys 2009; 54: 33-46.
90. Ballon DR, Flanary PL, Gladue DP, Konopka JB, Dohlman HG, Thorner J. DEP-domain-mediated regulation of GPCR signaling responses. Cell 2006; 126: 1079-93.
91. Drenan RM, Doupnik CA, Boyle MP, et al. Palmitoylation regulates plasma membrane-nuclear shuttling of R7BP, a novel membrane anchor for the RGS7 family. J Cell Biol 2005; 169: 623-33.
92. Martemyanov KA, Yoo PJ, Skiba NP, Arshavsky VY. R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family. J Biol Chem 2005; 280: 5133-6.
93. Song JH, Waataja JJ, Martemyanov KA. Subcellular targeting of RGS9-2 is controlled by multiple molecular determinants on its membrane anchor, R7BP. J Biol Chem 2006; 281: 15361-9.
94. Anderson GR, Lujan R, Semenov A, et al. Expression and localization of RGS9-2/G 5/R7BP complex in vivo is set by dynamic control of its constitutive degradation by cellular cysteine proteases. J Neurosci 2007; 27: 14117-14127.
95. Snow BE, Krumins AM, Brothers GM, et al. A G protein g subunit-like domain shared between RGS11 and other RGS proteins specifies binding to G 5 subunits. Proc Natl Acad Sci USA 1998; 95: 13307-12.
96. Chen C-K, Eversole-Cire P, Zhang H, et al. Instability of GGL domain-containing RGS proteins in mice lacking the G proteinsubunit G 5. Proc Natl Acad Sci USA 2003; 100: 6604-9.
97. He W, Lu L, Zhang X, et al. Modules in the photoreceptor RGS9-1.G 5L GTPase-accelerating protein complex control effector coupling, GTPase acceleration, protein folding, and stability. J Biol Chem 2000; 275: 37093-100.
98. Witherow DS, Wang Q, Levay K, et al. Complexes of the G protein subunit G 5 with the regulators of G protein signaling RGS7 and RGS9. Characterization in native tissues and in transfected cells. J Biol Chem 2000; 275: 24872-80.
99. Lan KL, Zhong H, Nanamori M, Neubig RR. Rapid kinetics of regulator of G-protein signaling (RGS)-mediated G i and G o deactivation. Ga specificity of RGS4 and RGS7. J Biol Chem 2000; 275: 33497-503.
100. Posner BA, Gilman AG, Harris BA. Regulators of G protein signaling 6 and 7. Purification of complexes with G 5 and assessment of their effects on G protein-mediated signaling pathways. J Biol Chem 1999; 274: 31087-93.
101. Granneman JG, Zhai Y, Zhu Z, et al. Molecular characterization of human and rat RGS 9L, a novel splice variant enriched in dopamine target regions, and chromosomal localization of the RGS 9 gene. Mol Pharmacol 1998; 54: 687-94.
102. Rahman Z, Gold SJ, Potenza MN, et al. Cloning and characterization of RGS9-2: A striatal-enriched alternatively spliced product of the RGS9 gene. J Neurosci 1999; 19: 2016-26.
103. Kim KJ, Moriyama K, Han KR, et al. Differential expression of the regulator of G protein signaling RGS9 protein in nociceptive pathways of different age rats. Brain Res Dev Brain Res 2005; 160: 28-39.
104. Psifogeorgou K, Papakosta P, Russo SJ, et al. RGS9-2 is a negative modulator of mu-opioid receptor function. J Neurochem 2007; 103: 617-25.
105. Garzon J, Rodriguez-Munoz M, Lopez-Fando A, Sanchez-Blazquez P. Activation of-opioid receptors transfers control of G subunits to the regulator of G-protein signaling RGS9-2: Role in receptor desensitization. J Biol Chem 2005; 280: 8951-60.
106. Garzon J, Lopez-Fando A, Sanchez-Blazquez P. The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at muopioid receptors. Neuropsychopharmacology 2003; 28: 1983-90.
107. Sanchez-Blazquez P, Rodriguez-Diaz M, Lopez-Fando A, Rodriguez-Munoz M, Garzon J. The G 5 subunit that associates with the R7 subfamily of RGS proteins regulates-opioid effects. Neuropharmacology 2003; 45: 82-95.
108. Zachariou V, Georgescu D, Sanchez N, et al. Essential role for RGS9 in opiate action. Proc Natl Acad Sci USA 2003; 100: 13656-61.
109. Shinohara T, Dietzschold B, Craft CM, et al. Primary and secondary structure of bovine retinal S antigen (48-kDa protein). Proc Natl Acad Sci USA 1987; 84: 6975-9.
110. Yamaki K, Takahashi Y, Sakuragi S, Matsubara K. Molecular cloning of the S-antigen cDNA from bovine retina. Biochem Biophys Res Commun 1987; 142: 904-10.
111. Benovic JL, Kühn H, Weyand I, Codina J, Caron MG, Lefkowitz RJ. Functional desensitization of the isolated-adrenergic receptor by the-adrenergic receptor kinase: Potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc Natl Acad Sci USA 1987; 84: 8879-82.
112. Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. Arrestin: A protein that regulates-adrenergic receptor function. Science 1990; 248: 1547-50.
113. Murakami A, Yajima T, Sakuma H, McLaren MJ, Inana G. Xarrestin: A new retinal arrestin mapping to the X chromosome. FEBS Lett 1993; 334: 203-9.
114. Attramadal H, Arriza JL, Aoki C, et al.-Arrestin2, a novel member of the arrestin/-arrestin gene family. J Biol Chem 1992; 267: 17882-90.
115. Parruti G, Peracchia F, Sallese M, et al. Molecular analysis of human-arrestin-1: Cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing. J Biol Chem 1993; 268: 9753-61.
116. Lohse MJ, Andexinger S, Pitcher J, et al. Receptor-specific desensitization with purified proteins. Kinase dependence and receptor specificity of-arrestin and arrestin in the 2-adrenergic receptor and rhodopsin systems. J Biol Chem 1992; 267: 8558-64.
117. Kohout TA, Lin FS, Perry SJ, Conner DA, Lefkowitz RJ. Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci USA 2001; 98: 1601-6.
118. Goodman OB, Krupnick JG, Santini F, et al.-Arrestin acts as a clathrin adaptor in endocytosis of the 2-adrenergic receptor. Nature 1996; 383: 447-50.
119. Laporte SA, Oakley RH, Zhang J, et al. The 2-adrenergic receptor/barrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc Natl Acad Sci USA 1999; 96: 3712-7.
120. Raehal KM, Schmid CL, Groer CE, Bohn LM. Functional selectivity at the-opioid receptor: implications for understanding opioid analgesia and tolerance. Pharmacol Rev 2011; 63: 1001-19.
121. Zhang X, Wang F, Chen X, Chen Y, Ma L. Post-endocytic fates of-opioid receptor are regulated by GRK2-mediated receptor phosphorylation and distinct-arrestin isoforms. J Neurochem 2008; 106: 781-92.
122. Rozenfeld R, Devi LA. Receptor heterodimerization leads to a switch in signaling:-Arrestin2-mediated ERK activation byopioid receptor heterodimers. FASEB J 2007; 21: 2455-65.
123. Bohn LM, Gainetdinov RR, Caron MG. G protein-coupled receptor kinase/-arrestin systems and drugs of abuse: psychostimulant and opiate studies in knockout mice. Neuromolecular Med 2004; 5: 41-50.
124. Gurevich EV, Benovic JL, Gurevich VV. Arrestin2 and arrestin3 are differentially expressed in the rat brain during postnatal development. Neuroscience 2002; 109: 421-36.
125. Oakley RH, Laporte SA, Holt JA, Caron MG, Barak LS. Differential affinities of visual arrestin, arrestin1, and arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J Biol Chem 2000; 275: 17201-10.
126. Cheng ZJ, Yu QM, Wu YL, Ma L, Pei G. Selective interference of-arrestin 1 with and but not opioid receptor/G protein coupling. J Biol Chem 1998; 273: 24328-33.
127. Schulz R, Wehmeyer A, Murphy J, Schulz K. Phosducin,-arrestin and opioid receptor migration. Eur J Pharmacol 1999; 375: 349-57.
128. Zhang J, Ferguson SS, Barak LS, et al. Role for G protein-coupled receptor kinase in agonist-specific regulation of-opioid receptor responsiveness. Proc Natl Acad Sci USA 1998; 95: 7157-62.
129. Groer CE, Schmid CL, Jaeger AM, Bohn LM. Agonist-directed interactions with specific-arrestins determine-opioid receptor trafficking, ubiquitination, and dephosphorylation. J Biol Chem 2011; 286: 31731-41.
130. Bohn LM, Dykstra LA, Lefkowitz RJ, Caron MG, Barak LS. Relative opioid efficacy is determined by the complements of the G protein-coupled receptor desensitization machinery. Mol Pharmacol 2004; 66: 106-12.
131. Celver JP, Lowe J, Kovoor A, Gurevich VV, Chavkin C. Threonine 180 is required for G-protein-coupled receptor kinase 3-and-arrestin 2-mediated desensitization of the-opioid receptor in Xenopus oocytes. J Biol Chem 2001; 276: 4894-900.
132. Kovoor A, Celver JP, Wu A, Chavkin C. Agonist induced homologous desensitization of-opioid receptors mediated by G protein-coupled receptor kinases is dependent on agonist efficacy. Mol Pharmacol 1998; 54: 704-11.
133. Kovoor A, Nappey V, Kieffer BL, Chavkin C. and Opioid receptors are differentially desensitized by the coexpression ofadrenergic receptor kinase 2 and-arrestin 2 in Xenopus oocytes. J Biol Chem 1997; 272: 27605-11.
134. Lowe JD, Celver JP, Gurevich VV, Chavkin C.-Opioid receptors desensitize less rapidly than-opioid receptors due to less efficient activation of arrestin. J Biol Chem 2002; 277: 15729-35.
135. Zheng H, Loh HH, Law P-Y. Arrestin-dependent-opioid receptor-activated extracellular signal-regulated kinases (ERKs) translocate to nucleus in contrast to G protein-dependent ERK activation. Mol Pharmacol 2008; 73: 178-90.
136. Macey TA, Lowe JD, Chavkin C. Opioid receptor activation of ERK1/2 is GRK3 and arrestin dependent in striatal neurons. J Biol Chem 2006; 281: 34515-24.
137. Xu C, Hong M-H, Zhang L-S, et al. Serine 363 of the-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands. J Cell Sci 2010; 123: 4259-70.
138. Li JG, Luo LY, Krupnick JG, Benovic JL, Liu-Chen LY. U50,488H-induced internalization of the human opioid receptor involves a-arrestinand dynamin-dependent mechanism. Receptor internalization is not required for mitogen-activated protein kinase activation. J Biol Chem 1999; 274: 12087-94.
139. Li JG, Benovic JL, Liu-Chen LY. Mechanisms of agonist-induced down-regulation of the human-opioid receptor: internalization is required for down-regulation. Mol Pharmacol 2000; 58: 795-801.
140. Appleyard SM, Celver J, Pineda V, Kovoor A, Wayman GA, Chavkin C. Agonist-dependent desensitization of the opioid receptor by G protein receptor kinase and b-arrestin. J Biol Chem 1999; 274: 23802-7.
141. Bruchas MR, Macey TA, Lowe JD, Chavkin C. Opioid receptor activation of p38 MAPK is GRK3and arrestin-dependent in neurons and astrocytes. J Biol Chem 2006; 281: 18081-9.
142. McLennan GP, Kiss A, Miyatake M, et al. opioids promote the proliferation of astrocytes via G and-arrestin 2-dependent MAPK-mediated pathways. J Neurochem 2008; 107: 1753-65.
143. Bohn LM, Lefkowitz RJ, Caron MG. Differential mechanisms of morphine antinociceptive tolerance revealed in-arrestin-2 knockout mice. J Neurosci 2002; 22: 10494-500.
144. Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT. Enhanced morphine analgesia in mice lacking-arrestin 2. Science 1999; 286: 2495-8.
145. Przewlocka B, Sieja A, Starowicz K, Maj M, Bilecki W, Przewlocki R. Knockdown of spinal opioid receptors by antisense targeting-arrestin reduces morphine tolerance and allodynia in rat. Neurosci Lett 2002; 325: 107-10.
146. Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG.-Opioid receptor desensitization by-arrestin-2 determines morphine tolerance but not dependence. Nature 2000; 408: 720-3.
147. Raehal KM, Bohn LM. The role of-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology 2011; 60: 58-65.
148. Bohn LM, Gainetdinov RR, Sotnikova TD, et al. Enhanced rewarding properties of morphine, but not cocaine, in-arrestin-2 knock-out mice. J Neurosci 2003; 23: 10265-73.
149. Ohsawa M, Mizoguchi H, Narita M, Nagase H, Dun NJ, Tseng LF. Involvement of-arrestin-2 in modulation of the spinal antinociception induced by-opioid receptor agonists in the mouse. Neurosci Lett 2003; 346: 13-6.
150. Bruchas MR, Land BB, Aita M, et al. Stress-induced p38 mitogenactivated protein kinase activation mediates-opioid-dependent dysphoria. J Neurosci 2007; 27: 11614-23.
151. Willets JM, Challiss RAJ, Nahorski SR. Non-visual GRKs: are we seeing the whole picture? Trends Pharmacol Sci 2003; 24: 626-33.
152. Johnson EA, Oldfield S, Braksator E, et al. Agonist-selective mechanisms of-opioid receptor desensitization in human embryonic kidney 293 cells. Mol Pharmacol 2006; 70: 676-85.
153. Wang HL. A cluster of Ser/Thr residues at the C-terminus ofopioid receptor is required for G protein-coupled receptor kinase 2-mediated desensitization. Neuropharmacology 2000; 39: 353-63.
154. Bailey CP, Oldfield S, Llorente J, et al. Involvement of PKC a and G-protein-coupled receptor kinase 2 in agonist-selective desensitization of-opioid receptors in mature brain neurons. Br J Pharmacol 2009; 158: 157-64.
155. Hull LC, Llorente J, Gabra BH, et al. The effect of protein kinase C and G protein-coupled receptor kinase inhibition on tolerance induced by-opioid agonists of different efficacy. J Pharmacol Exp Ther 2010; 332: 1127-35.
156. Li AH, Wang HL. G protein-coupled receptor kinase 2 mediatesopioid receptor desensitization in GABAergic neurons of the nucleus raphe magnus. J Neurochem 2001; 77: 435-44.
157. Doll C, Konietzko J, Poll F, Koch T, Hollt V, Schulz S. Agonistselective patterns of-opioid receptor phosphorylation revealed by phosphosite-specific antibodies. Br J Pharmacol 2011; 164: 298-307.
158. Doll C, Poll F, Peuker K, Loktev A, Gluck L, Schulz S. Deciphering-opioid receptor phosphorylation and dephosphorylation in HEK293 cells. Br J Pharmacol 2012.
159. Raehal KM, Schmid CL, Medvedev IO, Gainetdinov RR, Premont RT, Bohn LM. Morphine-induced physiological and behavioral responses in mice lacking G protein-coupled receptor kinase 6. Drug Alcohol Depend 2009; 104: 187-96.
160. Melief EJ, Miyatake M, Bruchas MR, Chavkin C. Ligand-directed c-Jun N-terminal kinase activation disrupts opioid receptor signaling. Proc Natl Acad Sci USA 2010; 107: 11608-13.
161. Terman GW, Jin W, Cheong Y-P, et al. G-protein receptor kinase 3 (GRK3) influences opioid analgesic tolerance but not opioid withdrawal. Br J Pharmacol 2004; 141: 55-64.
162. Gainetdinov RR, Bohn LM, Sotnikova TD, et al. Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice. Neuron 2003; 38: 291-303.
163. Hasbi A, Polastron J, Allouche S, Stanasila L, Massotte D, Jauzac P. Desensitization of the-opioid receptor correlates with its phosphorylation in SK-N-BE cells: involvement of a G proteincoupled receptor kinase. J Neurochem 1998; 70: 2129-38.
164. Li J, Xiang B, Su W, Zhang X, Huang Y, Ma L. Agonist-induced formation of opioid receptor-G protein-coupled receptor kinase (GRK)-G complex on membrane is required for GRK2 function in vivo. J Biol Chem 2003; 278: 30219-26.
165. Zhang J, Ferguson SS, Law PY, Barak LS, Caron MG. Agonistspecific regulation of-opioid receptor trafficking by G proteincoupled receptor kinase and-arrestin. J Recept Signal Transduct Res 1999; 19: 301-13.
166. Guo J, Wu Y, Zhang W, et al. Identification of G protein-coupled receptor kinase 2 phosphorylation sites responsible for agoniststimulated-opioid receptor phosphorylation. Mol Pharmacol 2000; 58: 1050-6.
167. Schulz R, Wehmeyer A, Schulz K. Opioid receptor types selectively cointernalize with G protein-coupled receptor kinases 2 and 3. J Pharmacol Exp Ther 2002; 300: 376-84.
168. Willets J, Kelly E. Desensitization of endogenously expressedopioid receptors: no evidence for involvement of G protein-coupled receptor kinase 2. Eur J Pharmacol 2001; 431: 133-41.
169. McLaughlin JP, Xu M, Mackie K, Chavkin C. Phosphorylation of a carboxyl-terminal serine within the-opioid receptor produces desensitization and internalization. J Biol Chem 2003; 278: 34631-40.
170. Schulz R, Wehmeyer A, Schulz K. Visualizing preference of G protein-coupled receptor kinase 3 for the process of-opioid receptor sequestration. Mol Pharmacol 2002; 61: 1444-52.
171. McLaughlin JP, Myers LC, Zarek PE, et al. Prolonged opioid receptor phosphorylation mediated by G-protein receptor kinase underlies sustained analgesic tolerance. J Biol Chem 2004; 279: 1810-8.
172. Feng B, Li Z, Wang JB. Protein kinase C-mediated phosphorylation of the-opioid receptor and its effects on receptor signaling. Mol Pharmacol 2011; 79: 768-75.
173. Levitt ES, Williams JT. Morphine desensitization and cellular tolerance are distinguished in rat locus coeruleus neurons. Mol Pharmacol 2012.
174. Smith FL, Gabra BH, Smith PA, Redwood MC, Dewey WL. Determination of the role of conventional, novel and atypical PKC isoforms in the expression of morphine tolerance in mice. Pain 2007; 127: 129-39.
175. Xiang B, Yu GH, Guo J, et al. Heterologous activation of protein kinase C stimulates phosphorylation of-opioid receptor at serine 344, resulting in-arrestinand clathrin-mediated receptor internalization. J Biol Chem 2001; 276: 4709-16.
176. Kenakin T. Functional selectivity and biased receptor signaling. J Pharmacol Exp Ther 2011; 336: 296-302.
177. Urban JD, Clarke WP, von Zastrow M, et al. Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther 2007; 320: 1-13.
178. Arden JR, Segredo V, Wang Z, Lameh J, Sadée W. Phosphorylation and agonist-specific intracellular trafficking of an epitope-tagged-opioid receptor expressed in HEK 293 cells. J Neurochem 1995; 65: 1636-45.
179. Pradhan AA, Smith ML, Kieffer BL, Evans CJ. Ligand-directed signaling within the opioid receptor family. Br J Pharmacol 2012; 167: 960-969.
180. Varga EV, Navratilova E, Stropova D, Jambrosic J, Roeske WR, Yamamura HI. Agonist-specific regulation of the-opioid receptor. Life Sci 2004; 76: 599-612.
181. Kane BE, Svensson B, Ferguson DM. Molecular recognition of opioid receptor ligands. AAPS J 2006; 8: E126-37.
182. Audet N, Charfi I, Mnie-Filali O, et al. Differential association of receptor-G complexes with-arrestin2 determines recycling bias and potential for tolerance of opioid receptor agonists. J Neurosci 2012; 32: 4827-40.
183. Haberstock-Debic H, Wein M, Barrot M, et al. Morphine acutely regulates opioid receptor trafficking selectively in dendrites of nucleus accumbens neurons. J Neurosci 2003; 23: 4324-32.
184. Whistler JL, Chuang HH, Chu P, Jan LY, von Zastrow M. Functional dissociation of opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction. Neuron 1999; 23: 737-46.
185. Whistler JL, von Zastrow M. Morphine-activated opioid receptors elude desensitization by-arrestin. Proc Natl Acad Sci USA 1998; 95: 9914-9.
186. Li Y, Liu X, Liu C, et al. Improvement of morphine-mediated analgesia by inhibition of-arrestin 2 expression in mice periaqueductal gray matter. Int J Mol Sci 2009; 10: 954-63.
187. Molinari P, Vezzi V, Sbraccia M, et al. Morphine-like opiates selectively antagonize receptor-arrestin interactions. J Biol Chem 2010; 285: 12522-35.
188. Frölich N, Dees C, Paetz C, et al. Distinct pharmacological properties of morphine metabolites at Gi-protein and-arrestin signaling pathways activated by the human-opioid receptor. Biochem Pharmacol 2011; 81: 1248-54.
189. McPherson J, Rivero G, Baptist M, et al. Mu-opioid receptors: Correlation of agonist efficacy for signalling with ability to activate internalization. Mol Pharmacol 2010; 78: 756-66.
190. Rivero G, Llorente J, McPherson J, et al. Endomorphin-2: a biased agonist at the-opioid receptor. Mol Pharmacol 2012; 82: 178-88.
191. Groer CE, Tidgewell K, Moyer RA, et al. An opioid agonist that does not induce-opioid receptor-arrestin interactions or receptor internalization. Mol Pharmacol 2007; 71: 549-57.
192. Lamb K, Tidgewell K, Simpson DS, Bohn LM, Prisinzano TE. Antinociceptive effects of herkinorin, a MOP receptor agonist derived from salvinorin A in the formalin test in rats. Drug Alcohol Depend 2012; 121: 181-8.
193. Zheng H, Chu J, Zhang Y, Loh HH, Law P-Y. Modulatingopioid receptor phosphorylation switches agonist-dependent signaling as reflected in PKC activation and dendritic spine stability. J Biol Chem 2011; 286: 12724-33.
194. Aguila B, Coulbault L, Davis A, et al.-Arrestin1-biased agonism at human-opioid receptor by peptidic and alkaloid ligands. Cell Signal 2011; 24: 699-707.
195. Pradhan AA, Walwyn W, Nozaki C, et al. Ligand-directed trafficking of the-opioid receptor in vivo: two paths toward analgesic tolerance. J Neurosci 2010; 30: 16459-68.
196. Pradhan AA, Becker JA, Scherrer G, et al. In vivo opioid receptor internalization controls behavioral effects of agonists. PloS One 2009; 4: e5425.
197. Bruchas MR, Yang T, Schreiber S, et al. Long-acting opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase. J Biol Chem 2007; 282: 29803-11.
198. Ingram SL, Traynor JR. Role of PKC in functional selectivity for desensitization at the-opioid receptor: From pharmacological curiosity to therapeutic potential. Br J Pharmacol 2009; 158: 154-6.
199. Lau EK, Trester-Zedlitz M, Trinidad JC, et al. Quantitative encoding of the effect of a partial agonist on individual opioid receptors by multisite phosphorylation and threshold detection. Sci Signal 2011; 4: ra52.
200. Chu J, Zheng H, Zhang Y, Loh HH, Law P-Y. Agonist-dependent-opioid receptor signaling can lead to heterologous desensitization. Cell Signal 2010; 22: 684-96.
201. Marie N, Aguila B, Hasbi A, Davis A, Jauzac P, Allouche S. Different kinases desensitize the human-opioid receptor (hDOPR) in the neuroblastoma cell line SK-N-BE upon peptidic and alkaloid agonists. Cell Signal 2008; 20: 1209-20.
202. Bradbury FA, Zelnik JC, Traynor JR. G protein independent phosphorylation and internalization of the-opioid receptor. J Neurochem 2009; 109: 1526-35.
203. Bruchas MR, Xu M, Chavkin C. Repeated swim stress induces opioid-mediated activation of extracellular signal-regulated kinase 1/2. Neuroreport 2008; 19: 1417-22.
204. Zhong H, Wade SM, Woolf PJ, Linderman JJ, Traynor JR, Neubig RR. A spatial focusing model for G protein signals. Regulator of G protein signaling (RGS) protien-mediated kinetic scaffolding. J Biol Chem 2003; 278: 7278-84.
205. Laroche G, Giguere PM, Roth BL, Trejo J, Siderovski DP. RNA interference screen for RGS protein specificity at muscarinic and protease-activated receptors reveals bidirectional modulation of signaling. Am J Physiol Cell Physiol 2010; 299: C654-64.
206. Psifogeorgou K, Terzi D, Papachatzaki MM, et al. A unique role of RGS9-2 in the striatum as a positive or negative regulator of opiate analgesia. J Neurosci 2011; 31: 5617-24.
207. Raehal KM, Bohn LM. Mu opioid receptor regulation and opiate responsiveness. AAPS J 2005; 7: E587-91.
208. Thal DM, Yeow RY, Schoenau C, Huber J, Tesmer JJ. Molecular mechanism of selectivity among G protein-coupled receptor kinase 2 inhibitors. Mol Pharmacol 2011; 80: 294-303.
209. Thal DM, Homan KT, Chen J, et al. Paroxetine is a direct inhibitor of G protein-coupled receptor kinase 2 and increases myocardial contractility. ACS Chem Biol 2012; 7: 1830-1839.
210. Grafstein-Dunn E, Young KH, Cockett MI, Khawaja XZ. Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain. Brain Res Mol Brain Res 2001; 88: 113-23.
211. Neubig RR, Siderovski DP. Regulators of G-protein signalling as new central nervous system drug targets. Nat Rev Drug Discov 2002; 1: 187-97.
212. Hooks SB, Martemyanov K, Zachariou V. A role of RGS proteins in drug addiction. Biochem Pharmacol 2008; 75: 76-84.
213. Traynor J. Regulator of G protein-signaling proteins and addictive drugs. Ann NY Acad Sci 2010; 1187: 341-52.
214. Traynor JR, Terzi D, Caldarone BJ, Zachariou V. RGS9-2: Probing an intracellular modulator of behavior as a drug target. Trends Pharmacol Sci 2009; 30: 105-11.
215. Traynor JR, Neubig RR. Regulators of G protein signaling & drugs of abuse. Mol Interv 2005; 5: 30-41.
216. Roman DL, Traynor JR. Regulators of G protein signaling (RGS) proteins as drug targets: modulating G-protein-coupled receptor (GPCR) signal transduction. J Med Chem 2011; 54: 7433-40.
217. Blazer LL, Zhang H, Casey EM, Husbands SM, Neubig RR. A nanomolar-potency small molecule inhibitor of regulator of Gprotein signaling proteins. Biochemistry 2011; 50: 3181-92.
218. Sjögren B, Neubig RR. Thinking outside of the RGS box: New approaches to therapeutic targeting of regulators of G protein signaling. Mol Pharmacol 2010; 78: 550-7.
219. Rajagopal S, Rajagopal K, Lefkowitz R. Teaching old receptors new tricks: Biasing seven-transmembrane receptors. Nat Rev Drug Discov 2010; 9: 373-86.
220. Rives M-L, Rossillo M, Liu-Chen L-Y, Javitch JA. 6' GNTI is a G protein-biased opioid receptor agonist that inhibits arrestin recruitment. J Biol Chem 2012; 287: 27050-4.