Angiotensin II and alpha-adrenergic agonists inhibit rat liver adenylate cyclase.

Abstract

Rat liver membranes were prepared according to a modified version of Neville's procedure ((1968) Biochin.Biophys.Acta 154, 540-552), and 5 mM EDTA was present at ail steps of the preparation.This type of preparation exhibited a GTP-dependent increase in adenylate cyclase activity in the presence of monovalent cations (Li' > Na' > K+).L-Epinephrine (100 p ~, in the presence of a P-adrenergic blocking agent) and Asn'-Val5-angiotensin 11 (1-100 n ~) inhibited the GTP plus ion-stimulated adenylate cyclase in a dose-dependent and not additive manner.But up to 1 PM, vasopressin did not inhibit the enzyme neither did it block the inhibitory effects of 1-epinephrine and angiotensin 11.Unlike prazosin, phentolamine, phenoxybenzamine, and yohimbine blocked adenylate cyclase inhibition by 1-epinephrine but did not affect that induced by angiotensin 11.This demonstrated that 1-epinephrine inhibited rat liver adenylate cyclase through an a-type of adrenoceptor different from the receptor mediating the angiotensin TI effect.Inhibition by angiotensin I1 was blocked by sarcosine'-1le"-angiotensin 11, a known competitive inhibitor of angiotensin 11.It is concluded from the present study that, of the three glycogenolytic agents tested, &epinephrine, angiotensin 11, and vasopressin, only Z-epinephrine and angiotensin II inhibit rat liver adenylate cyclase.These results, combined with the observation that the effect of epinephrine is mediated through an a & p e of adrenoceptor whereas phosphorylase activation by epinephrine is mediated through an crl-type, suggest that the observed inhibition of adenylate cyclase by epinephrine and angiotensin I1 is not directly related to the effects of these hormones on phosphorylase activation.' F. Assimacopoulos and E. H. Exton, personal communication.inhibition, respectively, were clearly different from each other suggests that the adenylate cyclase inhibition by angiotensin