PMID: 9535991May 16, 1998Paper

Agonist-induced desensitization and down-regulation of the human kappa opioid receptor expressed in Chinese hamster ovary cells

The Journal of Pharmacology and Experimental Therapeutics
J ZhuLee-Yuan Liu-Chen

Abstract

In this study, we examined whether the human kappa opioid receptor stably expressed in Chinese hamster ovary cells underwent desensitization and down-regulation after prolonged exposure to the agonist (-)U50,488H. Pretreatment with (-)U50,488H led to a reduction in the magnitude of increase in [35S]GTPgammaS binding by the subsequent application of (-)U50,488H. The extent of desensitization was related to duration of exposure and (-)U50,488H concentration. Pretreatment with (-)U50,488H also reduced the potency of (-)U50,488H in inhibiting forskolin-stimulated adenylate cyclase. In membranes of (-)U50,488H-pretreated cells, the affinity of (-)U50,488H was lower than that in the untreated control, and GTPgammaS had no effect on (-)U50,488H affinity, consistent with the notion of uncoupling of the receptor-G protein complex by (-)U50, 488H treatment. Down-regulation of the kappa opioid receptor also occurred on exposure to (-)U50,488H. Higher (-)U50,488H concentrations and/or longer incubation periods were required for down-regulation than for desensitization. The degree of down-regulation depended on the agonist concentration and incubation time. (-)U50,488H-induced desensitization and down-regulation were blocked by naloxone. (+...Continue Reading

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