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Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.

Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, Koch T, Evans CJ, Christie MJ.

Pharmacol Rev. 2013 Jan 15;65(1):223-54. doi: 10.1124/pr.112.005942. Print 2013 Jan. Review.


T394A Mutation at the μ Opioid Receptor Blocks Opioid Tolerance and Increases Vulnerability to Heroin Self-Administration in Mice.

Wang XF, Barbier E, Chiu YT, He Y, Zhan J, Bi GH, Zhang HY, Feng B, Liu-Chen LY, Wang JB, Xi ZX.

J Neurosci. 2016 Oct 5;36(40):10392-10403. Erratum in: J Neurosci. 2017 Mar 15;37(11):3102.


Mechanisms of rapid opioid receptor desensitization, resensitization and tolerance in brain neurons.

Dang VC, Christie MJ.

Br J Pharmacol. 2012 Mar;165(6):1704-1716. doi: 10.1111/j.1476-5381.2011.01482.x. Review.


Spinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.

Kibaly C, Lin HY, Loh HH, Law PY.

Pharmacol Res. 2017 May;119:153-168. doi: 10.1016/j.phrs.2017.01.033. Epub 2017 Feb 4.


RGS14 prevents morphine from internalizing Mu-opioid receptors in periaqueductal gray neurons.

Rodríguez-Muñoz M, de la Torre-Madrid E, Gaitán G, Sánchez-Blázquez P, Garzón J.

Cell Signal. 2007 Dec;19(12):2558-71. Epub 2007 Aug 15.


Direct association of Mu-opioid and NMDA glutamate receptors supports their cross-regulation: molecular implications for opioid tolerance.

Garzón J, Rodríguez-Muñoz M, Sánchez-Blázquez P.

Curr Drug Abuse Rev. 2012 Sep;5(3):199-226. Review.


Functional selectivity and time-dependence of μ-opioid receptor desensitization at nerve terminals in the mouse ventral tegmental area.

Lowe JD, Bailey CP.

Br J Pharmacol. 2015 Jan;172(2):469-81. doi: 10.1111/bph.12605. Epub 2014 Jul 1.


The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence.

Martini L, Whistler JL.

Curr Opin Neurobiol. 2007 Oct;17(5):556-64. Epub 2007 Dec 18. Review.


Morphine induces endocytosis of neuronal mu-opioid receptors through the sustained transfer of Galpha subunits to RGSZ2 proteins.

Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P, Garzón J.

Mol Pain. 2007 Jul 17;3:19.


Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.

He L, Whistler JL.

PLoS One. 2011;6(5):e19372. doi: 10.1371/journal.pone.0019372. Epub 2011 May 13.


Enhancement of morphine analgesic effect with induction of mu-opioid receptor endocytosis in rats.

Hashimoto T, Saito Y, Yamada K, Hara N, Kirihara Y, Tsuchiya M.

Anesthesiology. 2006 Sep;105(3):574-80.


The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation.

Petraschka M, Li S, Gilbert TL, Westenbroek RE, Bruchas MR, Schreiber S, Lowe J, Low MJ, Pintar JE, Chavkin C.

Neuroscience. 2007 Jun 8;146(4):1795-807. Epub 2007 Apr 30.


The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence.

Bao Y, Gao Y, Yang L, Kong X, Yu J, Hou W, Hua B.

Channels (Austin). 2015;9(5):235-43. doi: 10.1080/19336950.2015.1069450. Epub 2015 Jul 15. Review.


Mu-opioid receptor splice variants: sex-dependent regulation by chronic morphine.

Verzillo V, Madia PA, Liu NJ, Chakrabarti S, Gintzler AR.

J Neurochem. 2014 Sep;130(6):790-6. doi: 10.1111/jnc.12768. Epub 2014 Jun 11.


Functional selectivity at the μ-opioid receptor: implications for understanding opioid analgesia and tolerance.

Raehal KM, Schmid CL, Groer CE, Bohn LM.

Pharmacol Rev. 2011 Dec;63(4):1001-19. doi: 10.1124/pr.111.004598. Epub 2011 Aug 26. Review.


Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the micro-opioid receptor.

Schröder H, Wu DF, Seifert A, Rankovic M, Schulz S, Höllt V, Koch T.

Neuropharmacology. 2009 Mar;56(4):768-78. doi: 10.1016/j.neuropharm.2008.12.010.


Role of receptor internalization in opioid tolerance and dependence.

Koch T, Höllt V.

Pharmacol Ther. 2008 Feb;117(2):199-206. Epub 2007 Nov 17. Review.


Analgesic tolerance to high-efficacy agonists but not to morphine is diminished in phosphorylation-deficient S375A μ-opioid receptor knock-in mice.

Grecksch G, Just S, Pierstorff C, Imhof AK, Glück L, Doll C, Lupp A, Becker A, Koch T, Stumm R, Höllt V, Schulz S.

J Neurosci. 2011 Sep 28;31(39):13890-6. doi: 10.1523/JNEUROSCI.2304-11.2011.


How to design an opioid drug that causes reduced tolerance and dependence.

Berger AC, Whistler JL.

Ann Neurol. 2010 May;67(5):559-69. doi: 10.1002/ana.22002.


Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance.

Sim-Selley LJ, Scoggins KL, Cassidy MP, Smith LA, Dewey WL, Smith FL, Selley DE.

Br J Pharmacol. 2007 Aug;151(8):1324-33. Epub 2007 Jun 18.

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