Neutral antagonist activity of naltrexone and 6β-naltrexol in naïve and opioid-dependent C6 cells expressing a μ-opioid receptor

British Journal of Pharmacology

Volumn 156, Issue 7, 2009, Pages 1044-1053

  Divin, M F ^a   Bradbury, F A ^a   Carroll, F I ^b   Traynor, J R ^a,c  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b RTI INTERNATIONAL   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

Author keywords

opioid receptor; 6 naltrexol; Adenylyl cyclase; CAMP overshoot; Constitutive activity; CTAP; Inverse agonism; Naltrexone; Protean agonism; RTI 5989 25

Indexed keywords

ADENYLATE CYCLASE; CELL SURFACE RECEPTOR; CYCLIC AMP; DEXTRO PHENYLALANYLCYSTEINYLTYROSYL DEXTRO TRYPTOPHYLARGINYLTHREONYLPENICILLAMINYLTHREONINAMIDE 2,7 DISULFIDE; ENKEPHALIN[2 DEXTRO ALANINE 4 METHYLPHENYLALANINE 5 GLYCINE]; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); MORPHINE; MU OPIATE RECEPTOR; NALOXONE; NALTREXOL; NALTREXONE; OPIATE ANTAGONIST; RTI 5989 25; UNCLASSIFIED DRUG; 6 BETA HYDROXYNALTREXONE; 6 BETA-HYDROXYNALTREXONE; CTAP OCTAPEPTIDE; DELTA OPIATE RECEPTOR; DRUG DERIVATIVE; N (TRANS 4' (2 METHYLPHENYL) 2' BUTENYL) (3R,4R) DIMETHYL 4 (3 HYDROXYPHENYL)PIPERIDINE; N-(TRANS-4'-(2-METHYLPHENYL)-2'-BUTENYL)-(3R,4R)-DIMETHYL-4-(3-HYDROXYPHENYL)PIPERIDINE; PEPTIDE FRAGMENT; PIPERIDINE DERIVATIVE; SOMATOSTATIN;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CELL STRAIN HEK293; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG RECEPTOR BINDING; GLIOMA CELL; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RECEPTOR AFFINITY; SENSITIZATION; ANIMAL; BINDING COMPETITION; BIOSYNTHESIS; CELL LINE; CHEMISTRY; DRUG ANTAGONISM; DRUG POTENTIATION; INVERSE AGONISM; METABOLISM; PARTIAL AGONISM; RADIOASSAY; TUMOR CELL LINE;

ADENYLATE CYCLASE; ANIMALS; BINDING, COMPETITIVE; CELL LINE; CELL LINE, TUMOR; CYCLIC AMP; DRUG INVERSE AGONISM; DRUG PARTIAL AGONISM; ENKEPHALIN, ALA(2)-MEPHE(4)-GLY(5)-; HUMANS; MORPHINE; NALOXONE; NALTREXONE; PEPTIDE FRAGMENTS; PIPERIDINES; RADIOLIGAND ASSAY; RATS; RECEPTORS, OPIOID, DELTA; RECEPTORS, OPIOID, MU; SOMATOSTATIN;

EID: 67650653732     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2008.00035.x     Document Type: Article

References (50)

1. Abbruscato TJ, Thomas SA, Hruby VJ, Davis TP (1997). Blood-brain barrier permeability and bioavailability of a highly potent and mu-selective opioid antagonist, CTAP: comparison with morphine. J Pharmacol Exp Ther 280 : 402 409.
2. Arunlakshana O, Schild HO (1959). Some quantitative uses of drug antagonists. Br J Pharmacol Chemother 15 : 48 58.
3. Bagley EE, Chieng BCH, Christie MJ, Connor M (2005). Opioid tolerance in periaqueductal gray mouse neurons isolated from mice chronically treated with morphine. Br J Pharmacol 146 : 68 76.
4. 2 and the protein kinase inhibitors H7 and H8 on acute morphine dependence and antinociceptive tolerance in mice. J Pharmacol Exp Ther 277 : 484 490.
5. Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG (2000). Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408 : 720 723.
6. Bradford MM (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72 : 248 254.
7. Brillet K, Kieffer KL, Massotte D (2003). Enhanced spontaneous activity of the mu opioid receptor by cysteine mutations: characterization of a tool for inverse agonist screening. BMC Pharmacol 3 : 14.
8. Burford NT, Wang D, Sadee W (2000). G-protein coupling of μ-opioid receptors (OP3): elevated basal signaling activity. Biochem J 348 : 531 537.
9. Childers SR, Fleming LM, Selley DE, McNutt RW, Chang KJ (1993). BW373U86: a nonpeptidic delta-opioid agonist with novel receptor G-protein mediated actions in rat brain membranes and neuroblastoma cells. Mol Pharmacol 44 : 827 834.
10. Christie MJ (2008). Cellular adaptations to chronic opioids: tolerance, withdrawal and addiction. Br J Pharmacol 154 : 384 396.
11. 3. J Neurochem 99 : 1494 1504.
12. Clark MJ, Neubig RR, Traynor JR (2004). Endogenous regulator of G protein signaling protein suppress Go-dependent, μ-opioid agonist-mediated adenylyl cyclase supersensitization. J Pharmacol Exp Ther 310 : 215 222.
13. Connor M, Borgland SL, Christie MJ (1999). Continued morphine modulation of calcium channel currents in acutely isolated locus coeruleus neurons from morphine-dependent rats. Br J Pharmacol 128 : 1561 1569.
14. Costa T, Herz A (1989). Antagonists with negative intrinsic activity at δ-opioid receptors coupled to GTP-binding proteins. Proc Natl Acad Sci USA 86 : 7321 7325.
15. Divin MF, Ko MC, Traynor JR (2008). Comparison of the opioid antagonist properties of naltrexone and 6β-naltrexol in morphine-naïve and morphine-dependent mice. Eur J Pharmacol 583 : 48 55.
16. Johnson EE, Christie MJ, Connor M (2005). The role of opioid receptor phosphorylation and trafficking in adaptations to persistent opioid treatment. Neurosignals 14 : 290 302.
17. Kenakin T (2004). Efficacy as a vector: the relative prevalence and paucity of inverse agonism. Mol Pharmacol 65 : 2 11.
18. Ko MC, Divin MF, Lee H, Woods JH, Traynor JR (2006). Differential in vivo potencies of naltrexone and 6β-naltrexol in the monkey. J Pharmacol Exp Ther 316 : 772 779.
19. Lee KO, Akil H, Woods JH, Traynor JR (1999). Differential binding properties of oripavines at cloned mu- and delta-opioid receptors. Eur J Pharmacol 378 : 323 330.
20. Li J, Chen C, Huang P, Liu-Chen LY (2001). Inverse agonist up-regulates the constitutively active D3.49(164)Q mutant of the rat μ-opioid receptor by stabilizing the structure and blocking constitutive internalization and down-regulation. Mol Pharmacol 60 : 1064 1075.
21. Lin S, Gether U, Kobilka BK (1996). Ligand stabilization of the β2-adrenergic receptor: effect of DTT on receptor conformation monitored by circular dichroism and fluorescence spectroscopy. Biochemistry 35 : 14445 14451. (Pubitemid 26423703)
22. Liu JG, Prather PL (2001). Chronic exposure to μ-opioid agonists produces constitutive activation of the μ-opioid receptors in direct proportion to the efficacy of the agonist used for pretreatment. Mol Pharmacol 60 : 53 62.
23. Maldonado R, Negus S, Koob GF (1992). Precipitation of morphine withdrawal syndrome in rats by administration of mu-, delta- and kappa-selective opioid antagonists. Neuropharmacology 31 : 1231 1241.
24. Milligan G (2003). Constitutive activity and inverse agonists of G protein coupled receptors: a current perspective. Mol Pharm 64 : 1271 1276.
25. Miserey-Lenkei S, Parnot C, Bardin S, Corvol P, Clauser E (2002). Constitutive internalization of constitutively active angiotensin II AT1A receptor mutants is blocked by inverse agonists. J Biol Chem 277 : 5891 5901.
26. Mundey MK, Ali A, Wilson VG (2000). Pharmacological examination of contractile responses of the guinea-pig isolated ileum produced by μ-opioid receptor antagonists in the presence of, and following exposure to, morphine. Br J Pharmacol 131 : 893 902.
27. Neilan CL, Akil H, Woods JH, Traynor JR (1999). Constitutive activity of the δ-opioid receptor expressed in C6 glioma cells: identification of non-peptide δ-inverse agonists. Br J Pharmacol 128 : 556 562.
28. Neubig RR (2007). Missing links: mechanisms of protean agonism. Mol Pharmacol 71 : 1200 1202.
29. Pedersen SE, Ross EM (1985). Functional activation of β-adrenergic receptors by thiols in the presence or absence of agonist. J Biol Chem 260 : 14150 14157.
30. Raehal KM, Lowery JJ, Bhamidipati CM, Paolino RM, Blair JR, Wang D et al. (2005). In vivo characterization of 6β-naltrexol, an opioid ligand with less inverse agonist activity compared with naltrexone and naloxone in opioid-dependent mice. J Pharmacol Exp Ther 313 : 1150 1162.
31. Sadee W, Wang Z (1995). Agonist induced constitutive receptor activation as a novel regulatory mechanism. In : Sharp BM, Friedman H, Eisenstein TK, Madden JJ (eds). The Brain Immune Axis and Substance Abuse. Plenum Press : New York, pp. 85 90.
32. Selley DE, Cao CC, Liu Q, Childers SR (2000). Effects of sodium on agonist efficacy for G-protein activation in μ-opioid receptor-transfected CHO cells and rat thalamus. Br J Pharmacol 130 : 987 996.
33. Shahrestanifar M, Wang WW, Howells RD (1996). Studies on inhibition of μ and δ opioid receptor binding by dithiothreitol and N-ethylmaleimide. J Biol Chem 271 : 5505 5512.
34. Sterious SN, Walker EA (2003). Potency differences for D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 as an antagonist of peptide and alkaloid μ-agonists in an antinociception assay. J Pharmacol Exp Ther 304 : 301 309.
35. Strange PG (2008). Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors. Br J Pharmacol 153 : 1353 1363.
36. 35S]thio)triphosphate to NG108-15 cell membranes: characterization of agonist and inverse agonist effects. J Pharmacol Exp Ther 283 : 1276 1284.
37. 2) on adenylyl cyclase activity: implications for μ-opioid receptor Gs coupling. J Pharmacol Exp Ther 310 : 256 262.
38. Walker EA (2006). In vivo pharmacological resultant analysis reveals noncompetitive interactions between opioid antagonists in the rat tail-withdrawal assay. Br J Pharmacol 149 : 1071 1082.
39. Walker EA, Sterious SN (2005). Opioid antagonists differ according to negative intrinsic efficacy in a mouse model of acute dependence. Br J Pharmacol 145 : 975 983.
40. Walwyn W, Evans CJ, Hales TG (2007). β-arrestin2 and cSrc regulate the constitutive activity and recycling of μ opioid receptors in dorsal root ganglion neurons. J Neurosci 27 : 5092 5102.
41. Wang D, Raehal KM, Bilsky EJ, Sadee W (2001). Inverse agonists and neutral antagonists at μ-opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence. J Neurochem 77 : 1590 1600.
42. Wang D, Raehal KM, Lin ET, Lowery JJ, Kieffer BL, Bilsky EJ et al. (2004). Basal signaling activity of μ-opioid receptor in mouse brain: role in narcotic dependence. J Pharmacol Exp Ther 308 : 512 520.
43. Wang D, Sun X, Sadee W (2007a). Different effects of opioid antagonists on μ-, δ-, and κ-opioid receptors with and without agonist pretreatment. J Pharmacol Exp Ther 321 : 544 552.
44. Wang H, Guang W, Barbier E, Shapiro P, Wang JB (2007b). Mu opioid receptor mutant, T394A, abolishes opioid-mediated adenylyl cyclase superactivation. Neuroreport 18 : 1969 1973.
45. Wang Z, Bilsky EJ, Porreca F, Sadee W (1994). Constitutive mu opioid receptor activation as a regulatory mechanism underlying narcotic tolerance and dependence. Life Sci 54 : PL339 PL350.
46. Wang Z, Bilsky EJ, Xang D, Porreca F, Sadee W (1999). 3-Isobutyl-1-methylxanthine inhibits basal μ-opioid receptor phosphorylation and reverses acute morphine tolerance and dependence in mice. Eur J Pharmacol 371 : 1 9.
47. Watts VJ, Neve KA (2005). Sensitization of adenylate cyclase by Gαi/o-coupled receptors. Pharmacol Ther 106 : 405 421.
48. Yabaluri N, Medzihradsky F (1997). Down-regulation of the μ-opioid receptor by full but not partial agonists is independent of G protein coupling. Mol Pharmacol 52 : 896 902.
49. Zaki PA, Keith DE, Jr., Thomas JB, Carroll FI, Evans CJ (2001). Agonist-, antagonist-, and inverse agonist-regulated trafficking of the δ-opioid receptor correlates with, but does not require, G protein activation. J Pharmacol Exp Ther 298 : 1015 1020.
50. Zhao H, Loh H, Law PY (2006). Adenylyl cyclase superactivation induced by long-term treatment with opioid agonists is dependent on receptor localization within lipid rafts and is independent of receptor internalization. Mol Pharmacol 69 : 1421 1432.