Novel GPCR paradigms at the μ-opioid receptor

British Journal of Pharmacology

Volumn 172, Issue 2, 2015, Pages 287-296

  Thompson, G L ^a   Kelly, E ^b   Christopoulos, A ^a   Canals, M ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

allosterism; biased agonism; GPCR; opioid receptor

Indexed keywords

ANALGESIC AGENT; G PROTEIN COUPLED RECEPTOR; MU OPIATE RECEPTOR; LIGAND; NARCOTIC ANALGESIC AGENT;

ALLOSTERISM; CELL ACTIVATION; CELL COMPOSITION; CONFORMATIONAL TRANSITION; DRUG SAFETY; INTRACELLULAR SIGNALING; LIGAND BINDING; NONHUMAN; PROTEIN CONFORMATION; PROTEIN DETERMINATION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; RECEPTOR AFFINITY; REVIEW; STRUCTURE ACTIVITY RELATION; AGONISTS; ANIMAL; DRUG DEVELOPMENT; HUMAN; METABOLISM; PAIN;

ANALGESICS, OPIOID; ANIMALS; DRUG DISCOVERY; HUMANS; LIGANDS; PAIN; RECEPTORS, OPIOID, MU;

EID: 84920200051     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12600     Document Type: Review

References (60)

1. Akgün E, Javed MI, Lunzer MM, Smeester BA, Beitz AJ, Portoghese PS, (2013). Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception. Proc Natl Acad Sci USA 110: 11595-11599.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013). The Concise Guide to PHARMACOLOGY 2013/14: G Protein-Coupled Receptors. Br J Pharmacol 170: 1459-1581.
3. Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, et al. (2011). Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proc Natl Acad Sci USA 108: 18488-18493.
4. Aragay AM, Ruiz-Gõmez A, Penela P, Sarnago S, Elorza A, Jiménez-Sainz MC, et al. (1998). G protein-coupled receptor kinase 2 (GRK2): mechanisms of regulation and physiological functions. FEBS Lett 430: 37-40.
5. Black J, Leff P, (1983). Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci 220: 141-162.
6. Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC, (2011). Cardiorenal actions of TRV120027, a novel β-arrestin-biased ligand at the angiotensin II type I receptor, in healthy and heart failure canines: a novel therapeutic strategy for acute heart failure. Circ Heart Fail 4: 770-778.
7. Bokoch M, Zou Y, Rasmussen S, Liu C, Nygaard R, Rosenbaum D, et al. (2010). Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. Nature 463: 108-112.
8. Borgland SL, (2003). Opioid agonists have different efficacy profiles for G protein activation, rapid desensitization, and endocytosis of mu-opioid receptors. J Biol Chem 278: 18776-18784.
9. Burford NT, Clark MJ, Wehrman TS, Gerritz SW, Banks M, O'Connell J, et al. (2013). Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor. Proc Natl Acad Sci USA 110: 10830-10835.
10. Butcher AJ, Prihandoko R, Kong KC, McWilliams P, Edwards JM, Bottrill A, et al. (2011). Differential G-protein-coupled receptor phosphorylation provides evidence for a signaling bar code. J Biol Chem 286: 11506-11518.
11. Canals M, Sexton PM, Christopoulos A, (2011). Allostery in GPCRs: 'MWC' revisited. Trends Biochem Sci 36: 663-672.
12. Chen X-T, Pitis P, Liu G, Yuan C, Gotchev D, Cowan CL, et al. (2013). Structure activity relationships and discovery of a G protein biased μ opioid receptor ligand, [(3-methoxythiophen-2-yl)methyl]({2-[(9 R)-9-(pyridin-2-yl)-6-oxaspiro- [4.5]decan-9-yl]ethyl})-amine (TRV130), for the treatment of acute severe pain. J Med Chem 56: 8019-8031.
13. Clark MJ, Traynor JR, (2006). Mediation of adenylyl cyclase sensitization by PTX-insensitive galpha oA, galphai1, galpha i2 or galpha i3. J Neurochem 99: 1494-1504.
14. Dang VC, Chieng B, Azriel Y, Christie MJ, (2011). Cellular morphine tolerance produced by arrestin-2-dependent impairment of -opioid receptor resensitization. J Neurosci 31: 7122-7130.
15. Deupi X, Kobilka BK, (2010). Energy landscapes as a tool to integrate GPCR structure, dynamics, and function. Physiology 25: 293-303.
16. DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, et al. (2013). A G protein-biased ligand at the -opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther 344: 708-717.
17. Doll C, Konietzko J, Pöll F, Koch T, Höllt V, Schulz S, (2011). Agonist-selective patterns of μ-opioid receptor phosphorylation revealed by phosphosite-specific antibodies. Br J Pharmacol 164: 298-307.
18. Frölich N, Dees C, Paetz C, Ren X, Lohse MJ, Nikolaev VO, et al. (2011). Distinct pharmacological properties of morphine metabolites at G(i)-protein and β-arrestin signaling pathways activated by the human μ-opioid receptor. Biochem Pharmacol 81: 1248-1254.
19. Galandrin S, Oligny-Longpré G, Bouvier M, (2007). The evasive nature of drug efficacy: implications for drug discovery. Trends Pharmacol Sci 28: 423-430.
20. Ge X, Qiu Y, Loh HH, Law P-Y, (2009). GRIN1 regulates micro-opioid receptor activities by tethering the receptor and G protein in the lipid raft. J Biol Chem 284: 36521-36534.
21. Georgoussi Z, Georganta E-M, Milligan G, (2012). The other side of opioid receptor signalling: regulation by protein-protein interaction. Curr Drug Targets 13: 80-102.
22. Gregory KJ, Hall NE, Tobin AB, Sexton PM, Christopoulos A, (2010a). Identification of orthosteric and allosteric site mutations in M2 muscarinic acetylcholine receptors that contribute to ligand-selective signaling bias. J Biol Chem 285: 7459-7474.
23. Gregory KJ, Sexton PM, Christopoulos A, (2010b). Overview of receptor allosterism. Curr Protoc Pharmacol 51: 1-34.
24. Hoffmann C, Ziegler N, Reiner S, Krasel C, Lohse M, (2008). Agonist-selective, receptor-specific interaction of human P2Y receptors with beta-arrestin-1 and -2. J Biol Chem 283: 30933-30941.
25. Hofmann K, Scheerer P, Hildebrand P, Choe H-W, Park J, Heck M, et al. (2009). A G protein-coupled receptor at work: the rhodopsin model. Trends Biochem Sci 34: 540-552.
26. Johnson EA, Oldfield S, Braksator E, Gonzalez-Cuello A, Couch D, Hall KJ, et al. (2006). Agonist-selective mechanisms of mu-opioid receptor desensitization in human embryonic kidney 293 cells. Mol Pharmacol 70: 676-685.
27. Jordan BA, Devi LA, (1999). G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399: 697-700.
28. Just S, Illing S, Trester-Zedlitz M, Lau EK, Kotowski SJ, Miess E, et al. (2013). Differentiation of opioid drug effects by hierarchical multi-site phosphorylation. Mol Pharmacol 83: 633-639.
29. Keith DE, Murray SR, Zaki PA, Chu PC, Lissin DV, Kang L, et al. (1996). Morphine activates opioid receptors without causing their rapid internalization. J Biol Chem 271: 19021-19024.
30. Kenakin T, (2007). Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM receptors. Trends Pharmacol Sci 28: 407-415.
31. Kenakin T, (2011). Functional selectivity and biased receptor signaling. J Pharmacol Exp Ther 336: 296-302.
32. Kenakin T, Christopoulos A, (2013). Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat Rev Drug Discov 12: 205-216.
33. Keov P, Sexton PM, Christopoulos A, (2011). Allosteric modulation of G protein-coupled receptors: a pharmacological perspective. Neuropharmacology 60: 24-35.
34. Kieffer BL, Gavériaux-Ruff C, (2002). Exploring the opioid system by gene knockout. Prog Neurobiol 66: 285-306.
35. Koch T, Brandenburg L-O, Schulz S, Liang Y, Klein J, Höllt V, (2003). ADP-ribosylation factor-dependent phospholipase D2 activation is required for agonist-induced mu-opioid receptor endocytosis. J Biol Chem 278: 9979-9985.
36. Law PY, (2011). Opioid receptor signal transduction mechanisms. Opiate Receptors 23: 195-238.
37. Le Naour M, Akgün E, Yekkirala A, Lunzer MM, Powers MD, Kalyuzhny AE, et al. (2013). Bivalent ligands that target μ opioid (MOP) and cannabinoid1 (CB 1) receptors are potent analgesics devoid of tolerance. J Med Chem 56: 5505-5513.
38. Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, et al. (2012). Crystal structure of the μ-opioid receptor bound to a morphinan antagonist. Nature 485: 321-326.
39. Massotte D, Brillet K, Kieffer B, Milligan G, (2002). Agonists activate Gi1 alpha or Gi2 alpha fused to the human mu opioid receptor differently. J Neurochem 81: 1372-1382.
40. May L, Leach K, Sexton P, Christopoulos A, (2007). Allosteric modulation of G protein-coupled receptors. Annu Rev Pharmacol Toxicol 47: 1-51.
41. McPherson J, Rivero G, Baptist M, Llorente J, Al-Sabah S, Krasel C, et al. (2010). μ-opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization. Mol Pharmacol 78: 756-766.
42. Metcalf MD, Yekkirala AS, Powers MD, Kitto KF, Fairbanks CA, Wilcox GL, et al. (2012). The δ opioid receptor agonist SNC80 selectively activates heteromeric μ-δ opioid receptors. ACS Chem Neurosci 3: 505-509.
43. Milligan G, (2009). G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function. Br J Pharmacol 158: 5-14.
44. Molinari P, Vezzi V, Sbraccia M, Gro C, Riitano D, Ambrosio C, et al. (2010). Morphine-like opiates selectively antagonize receptor-arrestin interactions. J Biol Chem 285: 12522-12535.
45. Monod J, Wyman J, Changeux J-P, (1965). On the nature of allosteric transitions: a plausible model. J Mol Biol 88-118.
46. Raehal KM, Walker JKL, Bohn LM, (2005). Morphine side effects in beta-arrestin 2 knockout mice. J Pharmacol Exp Ther 314: 1195-1201.
47. Raehal KM, Schmid CL, Groer CE, Bohn LM, (2011). Functional selectivity at the μ-opioid receptor: implications for understanding opioid analgesia and tolerance. Pharmacol Rev 63: 1001-1019.
48. Rajagopal S, Ahn S, Rominger DH, Gowen-MacDonald W, Lam CM, DeWire SM, et al. (2011). Quantifying ligand bias at seven-transmembrane receptors. Mol Pharmacol 80: 367-377.
49. Rivero G, Llorente J, McPherson J, Cooke A, Mundell SJ, McArdle CA, et al. (2012). Endomorphin-2: a biased agonist at the μ-opioid receptor. Mol Pharmacol 82: 178-188.
50. Saidak Z, Blake-Palmer K, Hay DL, Northup JK, Glass M, (2009). Differential activation of G-proteins by μ-opioid receptor agonists. Br J Pharmacol 147: 671-680.
51. Shonberg J, Klein Herenbrink C, Lopez Munoz L, Christopoulos A, Scammells PJ, Capuano B, et al. (2013). A structure-activity analysis of biased agonism at the dopamine D2 receptor. J Med Chem 56: 9199-9221.
52. Stallaert W, Christopoulos A, Bouvier M, (2011). Ligand functional selectivity and quantitative pharmacology at G protein-coupled receptors. Expert Opin Drug Discov 6: 811-825.
53. Sternini C, Spann M, Anton B, Keith DE, Bunnett NW, von Zastrow M, et al. (1996). Agonist-selective endocytosis of mu opioid receptor by neurons in vivo. Proc Natl Acad Sci U S A 93: 9241-9246.
54. Tobin AB, Butcher AJ, Kong KC, (2008). Location, location, location... site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling. Trends Pharmacol Sci 29: 413-420.
55. Varamini P, Mansfeld FM, Blanchfield JT, Wyse BD, Smith MT, Toth I, (2012). Lipo-endomorphin-1 derivatives with systemic activity against neuropathic pain without producing constipation. PLoS ONE 7: e41909.
56. Wang D, (2005). Opioid receptor homo- and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer. Mol Pharmacol 67: 2173-2184.
57. van der Westhuizen ET, Breton B, Christopoulos A, Bouvier M, (2014). Quantification of ligand bias for clinically relevant 2-adrenergic receptor ligands: implications for drug taxonomy. Mol Pharmacol 85: 492-509.
58. Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, et al. (2013). Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 65: 223-254.
59. Yekkirala AS, Lunzer MM, McCurdy CR, Powers MD, Kalyuzhny AE, Roerig SC, et al. (2011). N-naphthoyl-beta-naltrexamine (NNTA), a highly selective and potent activator of μ/kappa-opioid heteromers. Proc Natl Acad Sci USA 108: 5098-5103.
60. Yekkirala AS, Banks ML, Lunzer MM, Negus SS, Rice KC, Portoghese PS, (2012). Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys. ACS Chem Neurosci 3: 720-727.