Agonist-Induced Phosphorylation of the κ-Opioid Receptor |
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Authors: | Suzanne M Appleyard Terrell A Patterson Wenzhen Jin Charles Chavkin |
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Institution: | Department of Pharmacology and; Neurobiology Graduate Program, University of Washington, Seattle, Washington, U.S.A. |
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Abstract: | Abstract: Antipeptide antibodies against the κ-opioid receptor were used to test whether acute or chronic exposure to κ agonists altered the phosphorylation state of the κ-opioid receptor. Immunoprecipitation of the κ receptor from guinea pig hippocampal slices preincubated in 32P]orthophosphoric acid revealed a basal phosphorylation of the κ-opioid receptor. The amount of 32P incorporation into the receptor was increased following a 75-min treatment with the κ agonist U50,488H. This effect was blocked by the selective κ receptor antagonist norbinaltorphimine. The time course of this change in the phosphorylation state of the receptor correlated with a desensitization of the electrophysiological response to κ agonists measured in the dentate gyrus of hippocampal slices. The phosphorylation state of the κ-opioid receptor was also elevated in brain slices from guinea pigs made tolerant to U50,488H by 5 days of continuous exposure and then maintained in κ agonist to avoid acute opiate withdrawal. The results of this study show that the κ-opioid receptor was phosphorylated in an agonist-dependent manner in brain slices taken from untreated and U50,488H-tolerant animals. |
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Keywords: | Opioid receptor G protein-coupled receptor phosphorylation Opioid tolerance Desensitization Kinase |
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