μ opiate receptors, the principal sites for opiate analgesia and reward, can display compensatory responses to opiate agonist drug administration. Agonist-induced K+ channel responses mediated by these receptors desensitize when examined in Xenopus oocyte expression systems. Mechanisms underlying such processes could include phosphorylation events similar to those reported to desensitize other G-protein-linked receptors. We used C-terminally directed anti-μ receptor antibodies to immunoprecipitate a phosphoprotein with size appropriate for the μ receptor from stably expressing Chinese hamster ovary cells. Phosphorylation of this μ opiate receptor protein was enhanced approximately 5-fold by treatment with the μ agonist morphine. The time course and dose-response relationships between μ receptor phosphorylation and agonist-induced desensitization display interesting parallels. Phosphorylation of μ opiate receptor protein is also enhanced ~5-fold by treatment with the protein kinase C activator phorbol 12- myristate 13-acetate. The protein kinase inhibitor staurosporine blocked the effect of phorbol 12-myristate 13-acetate on μ receptor phosphorylation. However, staurosporine failed to block morphine-induced phosphorylation. These observations suggest that several biochemical pathways can lead to μ receptor phosphorylation events that may include mechanisms involved in μ receptor desensitization.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Biological Chemistry|
|State||Published - 1996|
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