CATECHOLAMINE-INDUCED DESENSITIZATION IN TURKEY ERYTHROCYTES - CAMP MEDIATED IMPAIRMENT OF HIGH-AFFINITY AGONIST BINDING WITHOUT ALTERATION IN RECEPTOR NUMBER

Abstract

Desensitization of turkey erythrocyte adenylate cyclase by exposure of these cells to the .beta.-adrenergic agonist isoproterenol leads to a decrease in subsequent adenylate cyclase stimulation by isoproterenol, F- or Gpp(NH)p without any apparent loss or down regulation of receptors. The desensitization is associated with a functional uncoupling of the .beta.-adrenergic receptor. This evidenced by an impaired ability of receptors to form a high affinity, guanine nucleotide sensitive complex with agonist as assessed by computer analysis of radioligand binding data. The changes in adenylate cyclase responsiveness and the alterations in receptor affinity for agonists are reproduced by incubation of turkey erythrocytes with the cAMP analog 8-bromo-cAMP. One possible mechanism for the development of desensitization in adenylate cyclase systems may be a cAMP mediated alteration of a component(s) of the .beta.-adrenergic receptor-adenylate cyclase complex which results in impaired receptor-cyclase coupling.