μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volumn 62, Issue , 2015, Pages 61-67

  Convertino, Marino ^a   Samoshkin, Alexander ^b   Gauthier, Josee ^c   Gold, Michael S ^d   Maixner, William ^c   Dokholyan, Nikolay V ^a   Diatchenko, Luda ^b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b MCGILL UNIVERSITY   (Canada)

^c UNIVERSITY OF NORTH CAROLINA   (United States)

^d UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

6TM MOR isoform; Drug discovery; Review; Opioid receptor

Indexed keywords

DIAMORPHINE; IODOBENZOYLNALOXAMIDE; IODOBENZOYLNALTREXAMIDE; METHADONE; MORPHINE; MORPHINE 6 GLUCURONIDE; MORPHINE DERIVATIVE; MU OPIATE RECEPTOR; MU OPIATE RECEPTOR 6; MU OPIATE RECEPTOR AGONIST; UNCLASSIFIED DRUG; ISOPROTEIN; NARCOTIC ANALGESIC AGENT;

ANALGESIC ACTIVITY; ANIMAL BEHAVIOR; ARTICLE; CELLULAR DISTRIBUTION; CHRONIC PAIN; DRUG CLASSIFICATION; DRUG EFFICACY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG RESEARCH; DRUG SAFETY; DRUG SELECTIVITY; DRUG SENSITIVITY; DRUG TARGETING; GENE; GENE STRUCTURE; GENETIC VARIABILITY; HUMAN; KNOCKOUT MOUSE; NONHUMAN; OPRM1 GENE; PHARMACODYNAMICS; PHARMACOGENETICS; POSTOPERATIVE PAIN; PROTEIN ANALYSIS; PROTEIN STRUCTURE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSMEMBRANE HELIX; ANIMAL; GENETICS; METABOLISM; PROTEIN CONFORMATION;

ANALGESICS, OPIOID; ANIMALS; HUMANS; PROTEIN CONFORMATION; PROTEIN ISOFORMS; RECEPTORS, OPIOID, MU;

EID: 84937974345     PISSN: 02785846     EISSN: 18784216     Source Type: Journal    
DOI: 10.1016/j.pnpbp.2014.11.009     Document Type: Article

References (63)

1. Alkorta I., Loew G.H. A 3D model of the delta opioid receptor and ligand-receptor complexes. Protein Eng 1996, 9:573-583.
2. Ballantyne J.C., Shin N.S. Efficacy of opioids for chronic pain: a review of the evidence. Clin J Pain 2008, 24:469-478.
3. Chang G., Chen L., Mao J. Opioid tolerance and hyperalgesia. Med Clin North Am 2007, 91:199-211.
4. Kim S.H., Stoicea N., Soghomonyan S., Bergese S.D. Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review. Front Pharmacol 2014, 108(5):1-9.
5. Middleton C., Harden Acquired pharmaco-dynamic opioid tolerance: a concept analysis. J J Adv Nurs 2014, 70(2):272-281.
6. Bohn L.M., Gainetdinov R.R., Lin F.T., Lefkowitz R.J., Caron M.G. Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 2000, 408:720-723.
7. Boise L.H., Gonzalez-Garcia M., Postema C.E., Ding L., Lindsten T., Turka L.A., et al. Bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993, 74:597-608.
8. Cadet P., Mantione K.J., Stefano G.B. Molecular identification and functional expression of mu 3, a novel alternatively spliced variant of the human mu opiate receptor gene. J Immunol 2003, 170:5118-5123.
9. Chu L.F., Angst M.S., Clark D. Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations. Clin J Pain 2008, 24:479-496.
10. Crain S.M., Shen K.F. Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance/dependence liability. Pain 2000, 84:121-131.
11. Crain S.M., Shen K.F. Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia. Brain Res 2001, 888:75-82.
12. Esmaeili-Mahani S., Shimokawa N., Javan M., Maghsoudi N., Motamedi F., Koibuchi N., et al. Low-dose morphine induces hyperalgesia through activation of G alphas, protein kinase C, and L-type Ca2+ channels in rats. J Neurosci Res 2008, 86:471-479.
13. Filizola M., Laakkonen L., Loew G.H. 3D modeling, ligand binding and activation studies of the cloned mouse delta, mu and kappa opioid receptors. Protein Eng 1999, 12:927-942.
14. Gris P., Gauthier J., Cheng P., Gibson D.G., Gris D., Laur O., et al. A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism. Mol Pain 2010, 6:33.
15. Hayashi T., Su T.P. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell 2007, 131:596-610.
16. Hermans E. Biological and pharmacological control of the multiplicity of coupling at G-protein-coupled receptors. Pharmacol Ther 2003, 99:25-44.
17. Herz A., Millan M.J. Opioids and opioid receptors mediating antinociception at various levels of the neuraxis. Physiol Bohemoslov 1990, 39:395-401.
18. Juni A., Klein G., Pintar J.E., Kest B. Nociception increases during opioid infusion in opioid receptor triple knock-out mice. Neuroscience 2007, 147:439-444.
19. Karpa K.D., Lin R., Kabbani N., Levenson R. The dopamine D3 receptor interacts with itself and the truncated D3 splice variant d3nf: D3-D3nf interaction causes mislocalization of D3 receptors. Mol Pharmacol 2000, 58:677-683.
20. Kayser V., Besson J.M., Guilbaud G. Paradoxical hyperalgesic effect of exceedingly low doses of systemic morphine in an animal model of persistent pain (Freund's adjuvant-induced arthritic rats). Brain Res 1987, 414:155-157.
21. Kenakin T. Functional selectivity through protean and biased agonism: who steers the ship?. Mol Pharmacol 2007, 72:1393-1401.
22. Kream R.M., Sheehan M., Cadet P., Mantione K.J., Zhu W., Casares F., et al. Persistence of evolutionary memory: primordial six-transmembrane helical domain mu opiate receptors selectively linked to endogenous morphine signaling. Med Sci Monit 2007, 13:SC5-SC6.
23. Lee M., Silverman S.M., Hansen H., Patel V.B., Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician 2011, 14(2):145-161.
24. Low Y., Clarke C.F., Huh B.K. Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management. Singapore Med J 2012, 53(5):357-360.
25. Raehal K.M., Schmid C.L., Groer C.E., Bohn L.M. Functional selectivity at the μ-opioid receptor implications for understanding opioid analgesia and tolerance. Pharmacol Rev 2011, 63(4):1001-1019.
26. Morgan M.M., Christie M.J. Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human. Br J Pharmacol 2011, 164(4):1322-1334.
27. Levine J.D., Gordon N.C., Fields H.L. Naloxone dose dependently produces analgesia and hyperalgesia in postoperative pain. Nature 1979, 278:740-741.
28. North R.A. Membrane conductances and opioid receptor subtypes. NIDA Res Monogr 1986, 71:81-88.
29. Williams J.T., Christie M.J., Manzoni O. Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev 2001, 81:299-343.
30. Millan M.J. Descending control of pain. Prog Neurobiol 2002, 66:355-474.
31. Stanfa L., Dickenson A. Spinal opioid systems in inflammation. Inflamm Res 1995, 44:231-241.
32. Li X., Angst M.S., Clark J.D. A murine model of opioid-induced hyperalgesia. Brain Res Mol Brain Res 2001, 86:56-62.
33. Rubovitch V., Gafni M., Sarne Y. The mu opioid agonist DAMGO stimulates cAMP production in SK-N-SH cells through a PLC-PKC-Ca++ pathway. Brain Res Mol Brain Res 2003, 110:261-266.
34. Suarez-Roca H., Abdullah L., Zuniga J.R., Madison S., Maixner W. Multiphasic effect of morphine on the release of substance P from rat trigeminal nucleus caudalis slices. Brain Res 1992, 579:187-194.
35. Suarez-Roca H., Maixner W. Morphine produces a multiphasic effect on the release of substance P from rat trigeminal nucleus caudalis slices by activating different opioid receptor subtypes. Brain Res 1992, 579:195-203.
36. Suarez-Roca H., Maixner W. Morphine produces a bidirectional modulation of substance P release from cultured dorsal root ganglion. Neurosci Lett 1995, 194:41-44.
37. Wang H.Y., Friedman E., Olmstead M.C., Burns L.H. Ultra-low-dose naloxone suppresses opioid tolerance, dependence and associated changes in mu opioid receptor-G protein coupling and Gbetagamma signaling. Neuroscience 2005, 135:247-261.
38. Mostany R., Diaz A., Valdizan E.M., Rodriguez-Munoz M., Garzon J., Hurle M.A. Supersensitivity to mu-opioid receptor-mediated inhibition of the adenylyl cyclase pathway involves pertussis toxin-resistant Galpha protein subunits. Neuropharmacology 2008, 54:989-997.
39. Wang H.Y., Burns L.H. Gbetagamma that interacts with adenylyl cyclase in opioid tolerance originates from a Gs protein. J Neurobiol 2006, 66:1302-1310.
40. Pasternak G.W. Opioids and their receptors: are we there yet?. Neuropharmacol 2014, 76:198-203.
41. Nag K., Sultana N., Kato A., Hirose S. Headless splice variant acting as dominant negative calcitonin receptor. Biochem Biophys Res Commun 2007, 362:1037-1043.
42. Zhu X., Wess J. Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function. Biochem 1998, 37:15773-15784.
43. Pan Y.X., Xu J., Mahurter L., Bolan E., Xu M., Pasternak G.W. Generation of the mu opioid receptor (MOR-1) protein by three new splice variants of the Oprm gene. Proc Natl Acad Sci U S A 2001, 98:14084-14089.
44. Shabalina S.A., Zaykin D.V., Gris P., Ogurtsov A.Y., Gauthier J., Shibata K., et al. Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet 2009, 18:1037-1051.
45. Xu J., Xu M., Hurd Y.L., Pasternak G.W., Pan Y.X. Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene. J Neurochem 2009, 108:962-972.
46. Manglik A., Kruse A.C., Kobilka T.S., Thian F.S., Mathiesen J.M., Sunahara R.K., et al. Crystal structure of the micro-opioid receptor bound to a morphinan antagonist. Nature 2012, 485:321-326.
47. Pogozheva I.D., Lomize A.L., Mosberg H.I. Opioid receptor three-dimensional structures from distance geometry calculations with hydrogen bonding constraints. Biophys J 1998, 75:612-634.
48. Strahs D., Weinstein H. Comparative modeling and molecular dynamics studies of the delta, kappa and mu opioid receptors. Protein Eng 1997, 10:1019-1038.
49. Serohijos A.W., Chen Y., Ding F., Elston T.C., Dokholyan N.V. A structural model reveals energy transduction in dynein. Proc Natl Acad Sci U S A 2006, 103:18540-18545.
50. Serohijos A.W., Yin S., Ding F., Gauthier J., Gibson D.G., Maixner W., et al. Structural basis for mu-opioid receptor binding and activation. Structure 2011, 19:1683-1690.
51. Wise H. The roles played by highly truncated splice variants of G protein-coupled receptors. J Mol Signal 2012, 7:1-13.
52. Majumdar S., Grinnell S., Le R., Rouzic V., Burgman M., Polikar L., et al. Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc Natl Acad Sci U S A 2011, 108:19778-19783.
53. Revankar C.M., Cimino D.F., Sklar L.A., Arterburn J.B., Prossnitz E.R. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 2005, 307:1625-1630.
54. Loh H.H., Liu H.C., Cavalli A., Yang W., Chen Y.F., Wei L.N. Mu opioid receptor knockout in mice: effects on ligand-induced analgesia and morphine lethality. Brain Res Brain Res Mol 1998, 54:321-326.
55. Matthes H.W., Maldonado R., Simonin F., Valverde O., Slowe S., Kitchen I., et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature 1996, 383:819-823.
56. Sora I., Takahashi N., Funada M., Ujike H., Revay R.S., Donovan D.M., et al. Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia. Proc Natl Acad Sci U S A 1997, 94:1544-1549.
57. Schuller A.G., King M.A., Zhang J., Bolan E., Pan Y.X., Morgan D.J., et al. Retention of heroin and morphine-6 beta-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1. Nat Neurosci 1999, 2:151-156.
58. Pan Y.X., Xu J., Xu M., Rossi G.C., Matulonis J.E., Pasternak G.W. Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions. Proc Natl Acad Sci U S A 2009, 106:4917-4922.
59. Majumdar S., Subrath J., Le Rouzic V., Polikar L., Burgman M., Nagakura K., et al. Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants. J Med Chem 2012, 55:6352-6362.
60. Majumdar S., Burgman M., Haselton N., Grinnel S., Ocampo J., Pasternak A.R., et al. Generation of novel radiolabelled opiates through site-selective iodination. Biorg Med Chem Lett 2001, 21:4001-4004.
61. Samoshkin A., Viet C.T., Convertino M., Maixner W., Dokholyan N.V., Schmidt B., et al. Structural and functional interaction between 6TM MOR isoform and b2 adrenoreceptor. International Narcotics Research Conference 2014, Montreal, Quebec, Canada 2014, 13-18. [July 13-18, 2014].
62. Pasternak G.W., Pan Y.X. Mu opioids and their receptors: evolution of a concept. Pharmacol Rev 2013, 65:1257-1317.
63. van Dorp E.L., Kest B., Kowalczyk W.J., Morariu A.M., Waxman A.R., Arout C.A., et al. Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology 2009, 110:1356-1363.