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Agonist‐Induced Phosphorylation of the κ‐Opioid Receptor
Author(s) -
Appleyard Suzanne M.,
Patterson Terrell A.,
Jin Wenzhen,
Chavkin Charles
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69062405.x
Subject(s) - agonist , chemistry , opioid receptor , endocrinology , medicine , receptor , phosphorylation , opioid , hippocampal formation , dentate gyrus , δ opioid receptor , pharmacology , biology , biochemistry
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 [ 32 P]orthophosphoric acid revealed a basal phosphorylation of the κ‐opioid receptor. The amount of 32 P 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.