Molecular Pharmacology, Vol 20, 585-591, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Desensitization of Adenylate Cyclase to Prostaglandin E₁ or 2-Chloroadenosine

¹ Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205

The hypothesis was examined that prolonged activation of adenylate cyclase can result in a decrease in the specific activity of the enzyme, much as prolonged inhibition of adenylate cyclase gradually leads to an increase in the specific activity of the enzyme. Activation of adenylate cyclase of NG1O8-15 neuroblastoma-glioma hybrid cells by prostaglandin E₁ resulted in the gradual loss of basal adenylate cyclase activity as well as enzyme activity stimulated by prostaglandin E₁, 2-chloroadenosine, NaF, or both prostaglandin E₁ and guanyl-5'-yl imidodiphosphate. Exposure of NG1O8-15 cells to 8-Br cyclic AMP also resulted in the loss of basal, prostaglandin E₁-stimulated, and 2-chloroadenosine-stimulated adenylate cyclase activities. Cyclohexamide had no effect on prostaglandin E₁-dependent desensitization of adenylate cyclase, but inhibited recovery of enzyme activity from the desensitized state. In contrast, exposure of NG1O8-15 cells to 2-chloroadenosine resulted in the rapid loss of response to 2-chloroadenosine with a halflife of 1.8 hr, but prostaglandin E₁-stimulated and basal enzyme activities decreased only slightly.

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