MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Koch, T.
Right arrow Articles by Höllt, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Koch, T.
Right arrow Articles by Höllt, V.

Vol. 58, Issue 2, 328-334, August 2000

Allelic Variation S268P of the Human µ-Opioid Receptor Affects Both Desensitization and G Protein Coupling1

Thomas Koch,2 Thomas Kroslak,2 Marco Averbeck, Peter Mayer, Helmut Schröder, Evelyn Raulf, and Volker Höllt

Department of Pharmacology and Toxicology, Otto-von-Guericke University, Magdeburg, Germany

The decrease in µ-opioid receptor activity after chronic agonist exposure (1 µM [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin) is largely due to kinase-mediated phosphorylation of intracellular receptor domains. We have recently shown that the substitution of two putative Ca2+/calmodulin-dependent protein kinase II (CaMK II) phosphorylation sites, S261 and S266, by alanines in the third intracellular loop of the rat µ-opioid receptor (rMOR1) confers resistance to CaMK II-induced receptor desensitization. In the present study, we show that the injection of active CaMK II in Xenopus laevis oocytes led to the desensitization of S261A but not S266A receptor mutant, indicating that S266 is the primary CaMK II phosphorylation site of the rMOR1. For the corresponding phosphorylation site in the human µ-opioid receptor (hMOR), an allelic variation S268P has been recently identified. After expression in X. laevis oocytes and human embryonic kidney 293 cells, this human S268P receptor and a corresponding rat S266P receptor mutant revealed a loss of CaMK II-induced receptor desensitization and a decreased G protein coupling compared with the wild-type receptors. Our results suggest that serines 266 (rMOR1) and 268 (hMOR) play crucial role in receptor desensitization and signaling and that the allelic variation S268P results in a human receptor type with a weaker but persistent G protein coupling after agonist treatment.

1 This study was supported by Grant 1895A/0025 (to T.K.) from the Land Sachsen-Anhalt, SFB 426 (V.H.), and Fonds der Chemischen Industrie (V.H.).

2 These authors contributed equally to this work.

Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
T. Koch, A. Widera, K. Bartzsch, S. Schulz, L.-O. Brandenburg, N. Wundrack, A. Beyer, G. Grecksch, and V. Hollt
Receptor Endocytosis Counteracts the Development of Opioid Tolerance
Mol. Pharmacol., January 1, 2005; 67(1): 280 - 287.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
C. Skarke, A. Kirchhof, G. Geisslinger, and J. Lotsch
Comprehensive Mu-Opioid-Receptor Genotyping by Pyrosequencing
Clin. Chem., March 1, 2004; 50(3): 640 - 644.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. L. Borgland, M. Connor, P. B. Osborne, J. B. Furness, and M. J. Christie
Opioid Agonists Have Different Efficacy Profiles for G Protein Activation, Rapid Desensitization, and Endocytosis of Mu-opioid Receptors
J. Biol. Chem., May 23, 2003; 278(21): 18776 - 18784.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Pfeiffer, T. Koch, H. Schroder, M. Laugsch, V. Hollt, and S. Schulz
Heterodimerization of Somatostatin and Opioid Receptors Cross-modulates Phosphorylation, Internalization, and Desensitization
J. Biol. Chem., May 24, 2002; 277(22): 19762 - 19772.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Kroslak, T. Koch, E. Kahl, and V. Hollt
Human Phosphatidylethanolamine-binding Protein Facilitates Heterotrimeric G Protein-dependent Signaling
J. Biol. Chem., October 19, 2001; 276(43): 39772 - 39778.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. Chavkin, J. P. McLaughlin, and J. P. Celver
Regulation of Opioid Receptor Function by Chronic Agonist Exposure: Constitutive Activity and Desensitization
Mol. Pharmacol., July 1, 2001; 60(1): 20 - 25.
[Full Text]

Home page
 Mol. Pharmacol.Home page
J. P. McLaughlin and C. Chavkin
Tyrosine Phosphorylation of the {micro}-Opioid Receptor Regulates Agonist Intrinsic Efficacy
Mol. Pharmacol., June 1, 2001; 59(6): 1360 - 1368.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
K. Befort, D. Filliol, F. M. Decaillot, C. Gaveriaux-Ruff, M. R. Hoehe, and B. L. Kieffer
A Single Nucleotide Polymorphic Mutation in the Human {micro}-Opioid Receptor Severely Impairs Receptor Signaling
J. Biol. Chem., January 26, 2001; 276(5): 3130 - 3137.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. M. Appleyard, J. P. McLaughlin, and C. Chavkin
Tyrosine Phosphorylation of the kappa -Opioid Receptor Regulates Agonist Efficacy
J. Biol. Chem., December 1, 2000; 275(49): 38281 - 38285.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Wang, J. M. Quillan, K. Winans, J. L. Lucas, and W. Sadee
Single Nucleotide Polymorphisms in the Human {micro} Opioid Receptor Gene Alter Basal G Protein Coupling and Calmodulin Binding
J. Biol. Chem., September 7, 2001; 276(37): 34624 - 34630.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics