Opioid regulation of Mu receptor internalisation: relevance to the development of tolerance and dependence

Lopez-Gimenez, J.F. and Milligan, G. (2010) Opioid regulation of Mu receptor internalisation: relevance to the development of tolerance and dependence. CNS and Neurological Disorders: Drug Targets, 9(5), pp. 616-626. (doi: 10.2174/187152710793361522) (PMID:20632966)

Abstract

Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence. Although aspects of this model are controversial, such observations suggest a number of approaches to further enhance the use of morphine as an analgesic.

• Item Type: Articles
• Keywords: Morphine, tolerance, dependence, receptor internalisation, desensitization
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lopez-Gimenez, Dr Juan and Milligan, Professor Graeme
• Authors: Lopez-Gimenez, J.F., and Milligan, G.
• Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: CNS and Neurological Disorders: Drug Targets
• Publisher: Bentham Science Publishers
• ISSN: 1871-5273
• ISSN (Online): 1996-3181
• Copyright Holders: Copyright © 2010 Bentham Science Publishers
• First Published: First published in CNS and Neurological Disorders: Drug Targets 9(5):616-626
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
48046	1	Molecular basis of the functional regulation of mu opioid receptors by co-expressed Gq/G11-coupled GPCRs	Graeme Milligan	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/G001200/1	Institute of Neuroscience and Psychology