Corticotropin-inhibiting peptide enhances aldosterone secretion by dispersed rat zona glomerulosa cells

Corticotropin-inhibiting peptide (CIP), the 7-38 fragment of human ACTH(1-3 9), is known to act as an antagonist of ACTH receptors. Accordingly, CIP ha s been found to inhibit ACTH-stimulated glucocorticoid secretion of dispers ed rat adrenocortical cells, without per se affecting the basal production. We confirmed these findings, but unexpectedly observed that CIP concentrat ion-dependently raised basal aldosterone secretion from fresh suspensions o f rat zona glomerulosa (ZG) cells, maximal effective concentration being 10 (-6) M. CIP (10(-6) M) partially reversed the ZG-cell response to ACTH, but not to the Ca2+-dependent agonists angiotensin-II (ANG-II) and K+. The asp ecific ANG-II-receptor antagonist saralasin (10(-6) M) blocked the aldoster one response of ZG cells to 10(-6) M CIP, and in the presence of the Ca2+-c hannel blocker verapamil CIP was ineffective. Collectively, these findings suggest that CIP enhances aldosterone secretion of rat ZG through a mechani sm involving the activation of ANG-II receptors and the consequent rise in the cytosolic Ca2+ concentration. They also stress that this side-effect of CIP must be taken into account in interpreting the results of investigatio ns on the adrenal cortex, where CIP has been employed as an ACTH-receptor a ntagonist. (C) 1998 Elsevier Science Ltd. All rights reserved.