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 Bushell, T.
Right arrow Articles by Miller, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bushell, T.
Right arrow Articles by Miller, R. J.

Vol. 61, Issue 1, 55-64, January 2002

Molecular Components of Tolerance to Opiates in Single Hippocampal Neurons

T. Bushell,1 T. Endoh, A. A. Simen, D. Ren, V. P. Bindokas, and R. J. Miller

Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois

We examined the effect of acute and chronic opioid treatment on synaptic transmission and µ-opioid receptor (MOR) endocytosis in cultures of naïve rat hippocampal neurons. Opioid agonists that activate MOR inhibited synaptic transmission at inhibitory but not excitatory autapses. [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), morphine, and methadone were all effective at blocking inhibitory transmission. These same drugs also reduced the amplitude of voltage-dependent Ca2+ currents in inhibitory but not excitatory neurons. Chronic treatment with all three opioids reduced the subsequent effects of a challenge with either the same drug or one of the others in individual autaptic neurons. Chronic treatment with DAMGO or methadone produced internalization of enhanced yellow fluorescent protein-tagged MOR expressed in hippocampal neurons within hours, whereas morphine produced internalization much more slowly, even when accompanied by overexpression of beta -arrestin-2. We conclude that DAMGO, methadone, and morphine all produce tolerance in single hippocampal neurons. Morphine-induced tolerance does not necessarily seem to involve receptor endocytosis.

1 Current address: Department of Biophysics, Imperial College of Science, Technology and Medicine, London SW7 2BZ, UK.

Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Physiol.Home page
T. Bushell
The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders
J. Physiol., May 15, 2007; 581(1): 7 - 16.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
Z. Zuo
The Role of Opioid Receptor Internalization and {beta}-Arrestins in the Development of Opioid Tolerance
Anesth. Analg., September 1, 2005; 101(3): 728 - 734.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. Haberstock-Debic, K.-A. Kim, Y. J. Yu, and M. von Zastrow
Morphine Promotes Rapid, Arrestin-Dependent Endocytosis of {micro}-Opioid Receptors in Striatal Neurons
J. Neurosci., August 24, 2005; 25(34): 7847 - 7857.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P. T. Toth, D. Ren, and R. J. Miller
Regulation of CXCR4 Receptor Dimerization by the Chemokine SDF-1{alpha} and the HIV-1 Coat Protein gp120: A Fluorescence Resonance Energy Transfer (FRET) Study
J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 8 - 17.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. Celver, M. Xu, W. Jin, J. Lowe, and C. Chavkin
Distinct Domains of the {micro}-Opioid Receptor Control Uncoupling and Internalization
Mol. Pharmacol., March 1, 2004; 65(3): 528 - 537.
[Abstract] [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 Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics