Opioid Regulation of Mu Receptor Internalisation: Relevance to the Development of Tolerance and Dependence

Title: Opioid Regulation of Mu Receptor Internalisation: Relevance to the Development of Tolerance and Dependence

Volume: 9 Issue: 5

Author(s): Juan F. Lopez-Gimenez and Graeme Milligan

Affiliation:

Keywords: morphine, tolerance, dependence, receptor internalisation, desensitization

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.

Cite this article as:

F. Lopez-Gimenez Juan and Milligan Graeme, Opioid Regulation of Mu Receptor Internalisation: Relevance to the Development of Tolerance and Dependence, CNS & Neurological Disorders - Drug Targets 2010; 9 (5) . https://dx.doi.org/10.2174/187152710793361522