Neurosignals 2005;14:290–302
(DOI:10.1159/000093044)

The Role of Opioid Receptor Phosphorylation and Trafficking in Adaptations to Persistent Opioid Treatment

Johnson E.E. · Christie M.J. · Connor M.
Pain Management Research Institute, Kolling Institute, University of Sydney at Royal North Shore Hospital, St. Leonards, Australia
email Corresponding Author


 goto top of outline Key Words

  • Opioid receptor trafficking
  • Phosphorylation
  • G-Protein-coupled receptor kinase
  • Morphine, chronic

 goto top of outline Abstract

μ-Opioid receptor activation underpins clinical analgesia and is the central event in the abuse of narcotics. Continued opioid use produces tolerance to the acute effects of the drug and adaptations that lead to physical and psychological dependence. Continued μ-receptor signaling provides the engine for these adaptations, with most evidence suggesting that chronic agonist treatment produces only limited alterations in primary μ-opioid receptor signaling. Here we examine agonist regulation of μ-opioid receptor function, and whether this is altered by chronic treatment. Receptor phosphorylation is thought to be the key initial event in agonist regulation of the μ-opioid receptor, providing a signal for acute receptor desensitization and also subsequent receptor resensitization. Morphine appears to produce qualitatively and quantitatively different μ-receptor phosphorylation than other agonists, but the consequences of this remain obscure, at least in neurons. There is no evidence that agonist-induced μ-opioid receptor phosphorylation changes in chronically morphine-treated animals, although receptor regulation appears to be altered. Thus, as receptor phosphorylation and resensitization appear to maintain continued signaling through the μ-opioid receptor, these two events are crucial in facilitating adaptations to chronic opioid treatment, and the possibility that agonist-specific phosphorylation can contribute to the development of different adaptations remains open.

Copyright © 2005 S. Karger AG, Basel


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 goto top of outline Author Contacts

Mark Connor
Pain Management Research Institute, E25
University of Sydney at Royal North Shore Hospital
St Leonards, NSW 2065 (Australia)
Tel. +61 2 9926 5184, Fax +61 2 9926 7659, E-Mail markc@med.usyd.edu.au


 goto top of outline Article Information

Received: October 25, 2005
Number of Print Pages : 13
Number of Figures : 2, Number of Tables : 0, Number of References : 96


 goto top of outline Publication Details

Neurosignals

Vol. 14, No. 6, Year 2005 (Cover Date: June 2006)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (print), 1424–8638 (Online)

For additional information: http://www.karger.com/NSG


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