Adrenocorticotropic hormone inhibits angiotensin II-stimulated inositol phosphate accumulation in rat adrenal glomerulosa cells

Abstract

Rat adrenal glomerulosa cells labelled for 18 h with [ 3H]inositol responded to angiotensin II with a dose-dependent stimulation of the accumulation of inositol monophosphate, inositol bisphosphate and inositol trisphosphate. Addition of adrenocorticotropic hormone (ACTH) (10 −7 M) reduced the maximum responses without altering the EC 50 values for angiotensin II. Thus, ACTH acted as a non-competitive inhibitor with respect to angiotensin II. No inhibition was observed in cells labelled for 2 h with [ 3H]inositol. Detailed examination of the inhibition showed that ACTH(1–24) was the most potent inhibitor, with ACTH(1–39) being 10-fold less potent. A mixture of α-melanocyte-stimulating hormone (α-MSH) (ACTH(1–13)) and corticotropin-like intermediate lobe peptide (ACTH(18–39)) was similarly inactive. ACTH(5–24) did not produce detectable inhibition. In terms of specificity, the receptor mediating ACTH inhibition of phosphatidylinositol turnover was similar to the receptor which mediated stimulation of aldosterone synthesis. Inhibition by ACTH was additive with inhibition produced by dibutyryl cAMP demonstrating that it was not mediated by rises in intracellular cAMP. ACTH inhibition also was additive with inhibition by the calcium channel blocker, nifedipine. These results demonstrate an interaction between ACTH receptors and angiotensin II receptors in adrenal glomerulosa cells at the level of their receptor-second messenger pathways.