Adrenomedullin and proadrenomedullin N-terminal 20 peptide inhibit agonist-stimulated aldosterone secretion of human adrenocortical cells, through a mechanism probably involving the impairment of calcium influx

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two hypotensive peptides, which are able to inhibit agonist-stimulated aldosterone secretion from adrenal zona glomerulosa. In this study we examined the effects of these two peptides on the aldosterone response of dispersed human adrenocortical cells to maximal effective concentrations of their main agonists. ADM (10-7 M) and PAMP (10-8 M) did not affect either basal or ACTH-stimulated aldosterone secretion, but they counteracted the secretory response to both 10-9 M angiotensin-II (ANG-II) (partial inhibition) and 10 mM K+ (complete inhibition). The Ca2+ ionophore A23187 (10-5 M) partially reversed the inhibitory effect of both peptides on aldosterone response to ANG-II, and abolished that on aldosterone response to K+. Collectively these findings provide indirect evidence that the mechanism underlying the aldosterone antisecretagogue action of ADM and PAMP may involve the impairment of the agonist-induced rise in the cytosolic Ca2+ concentration, and especially of Ca2+ influx.