AGONIST-INDUCED PHOSPHORYLATION OF THE KAPPA-OPIOID RECEPTOR

Antipeptide antibodies against the kappa-opioid receptor were used to test whether acute or chronic exposure to kappa agonists altered the p hosphorylation state of the kappa-opioid receptor. Immunoprecipitation of the kappa receptor from guinea pig hippocampal slices preincubated in [P-32] orthophosphoric acid revealed a basal phosphorylation of th e kappa-opioid receptor, The amount of P-32 incorporation into the rec eptor was increased following a 75-min treatment with the kappa agonis t U50,488H, This effect was blocked by the selective kappa receptor an tagonist norbinaltorphimine. The time course of this change in the pho sphorylation state of the receptor correlated with a desensitization o f the electrophysiological response to kappa agonists measured in the dentate gyrus of hippocampal slices, The phosphorylation state of the kappa-opioid receptor was also elevated in brain slices from guinea pi gs made tolerant to U50,488H by 5 days of continuous exposure and then maintained in kappa agonist to avoid acute opiate withdrawal, The res ults of this study show that the kappa-opioid receptor was phosphoryla ted in an agonist-dependent manner in brain slices taken from untreate d and U50,488H-tolerant animals.