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Access through your institution Buy or subscribe Opioid receptors belong to the large superfamily of G-protein-coupled receptors (GPCRs). The mechanisms for mediating the development of
tolerance and dependence to morphine are controversial. The ability of MOR agonists to promote endocytosis of MOR is not related linearly to the agonist activity. The net amount of a signal
that is transmitted to the cell is a function of both processes, a relationship termed 'relative activity versus endocytosis', or RAVE. Morphine has a high RAVE value because of an
inability to promote endocytosis. Endorphins and other opiate drugs have similar signalling efficacies, but have lower RAVE values because they induce endocytosis. Whistler and colleagues
reasoned that if prolonged signalling at MOR contributes to the development of tolerance, then lowering the RAVE value by reducing that prolonged signalling would reduce the unwanted side
effects. Consistent with this hypothesis, they showed that rats treated chronically with morphine plus the enkephalin, DAMGO (d-Ala2-MePhe4-Gly5-ol), which facilitates MOR endocytosis, had
reduced development of analgesic tolerance compared with rats treated with morphine alone. The present study shows that MOR can dimerize, as seen with other GPCRs, and proposes that this
dimerization is mechanistically important in influencing the endocytic properties of the receptor, thereby reducing the development of tolerance to morphine. This is a preview of
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ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL RESEARCH PAPER * He, L. et al. Regulation of
opioid receptor trafficking and morphine tolerance by receptor oligomerization. _Cell_ 108, 271–282 (2002) Article CAS Google Scholar FURTHER READING * Williams, J. T. et al. Cellular and
synaptic adaptations mediating opioid dependence. _Physiol. Rev._ 81, 299–343 (2001) Article CAS Google Scholar Download references Authors * Melanie Brazil View author publications You
can also search for this author inPubMed Google Scholar RELATED LINKS RELATED LINKS WEB SITES Whistler's laboratory Encyclopedia of Life Sciences opiates opiate receptors RIGHTS AND
PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Brazil, M. Ecstatic about RAVE. _Nat Rev Neurosci_ 3, 166 (2002). https://doi.org/10.1038/nrn761 Download citation *
Issue Date: 01 March 2002 * DOI: https://doi.org/10.1038/nrn761 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a
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