Adenosine 3′:5′-cyclic monophosphate production and steroidogenesis by isolated rat adrenal glomerulosa cells. Effects of angiotensin II and [Sar1,Ala8]angiotensin II

Abstract

Angiotensin II effects on cyclic[c]AMP production and steroid output were studied in a sensitive preparation of isolated rat adrenal glomerulosa cells. With increasing concentrations of angiotensin II logarithmic dose-response curves for aldosterone and cAMP production were similar. The minimum effective dose (0.2 nM) for stimulation of aldosterone production also significantly (P < 0.001) increased cAMP output. For both aldosterone and cAMP production, the peptide hormone concentration eliciting maximal response (0.2 .mu.M) and the ED50 values (1 nM) were the same; this is consistent with cAMP acting as an intracellular mediator for angiotensin II-stimulated aldosterone production by glomerulosa cells. The angiotensin II antagonist [Sar1,Ala8]angiotensin II inhibited angiotensin II-stimulated corticosterone and aldosterone production in these cells. An equimolar concentration of antagonist halved the response to 20 nM-angiotensin II, and complete inhibition was observed with 0.2 .mu.M-antagonist. In contrast, [Sar1,Ala8]angiotensin II had no effect on maximally stimulated steroidogenesis induced by serotonin and a raised extracellular K+ concentration. Increasing concentrations of [Sar1,Ala8]angiotensin II alone decreased corticosterone and aldosterone outputs significantly (P < 0.05) at concentrations of 20 nM and 2 nM of antagonist respectively. A significant (P < 0.001) decrease in cAMP production occurred with 2 .mu.M antagonist and this was comparable with the decrease in aldosterone production. Apparently [Sar1,Ala8]angiotensin II can independently affect glomerulosa-cell steroidogenesis, possibly by modulating adenylate cyclase activity.