Catecholamine induced subsensitivity of adenylate cyclase associated with loss of β adrenergic receptor binding sites

Abstract

Injection of frogs with β adrenergic catecholamines for 1-24 hr produces marked subsensitivity of the erythrocyte membrane adenylate cyclase [ATP pyrophosphate lyase (cyclizing); EC 4.6.1.1] to in vitro stimulation by isoproterenol. The subsensitization is specific for catecholamine stimulation, since basal and fluoride stimulated enzyme activity are unaffected. Maximum isoproterenol stimulated adenylate cyclase activity declines by 75% in the isoproterenol treated animals (P < 0.001). The concentration of isoproterenol causing 1/2 maximal activation of adenylate cyclase, however, is unaltered. (-)[3H]Alprenolol, a potent competitive β adrenergic antagonist, was used to study directly the β adrenergic receptor binding sites in the erythrocyte membranes from control and subsensitized animals. A highly significant (P < 0.005) 60% fall in the number of the β adrenergic receptor binding sites ('specific' (-)[3H]alprenolol binding sites) in the treated animals was found. The binding affinity of the sites was not markedly altered. These data suggest that β adrenergic catecholamines are able to regulate catecholamine sensitivity of tissues in vivo, by regulating the properties of the β adrenergic receptor binding sites.