Effects of adrenomedullin and proadrenomedullin N-terminal 20 peptide on rat zona glomerulosa

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) derive from a 185-amino acid prohormone, called preproadrenomedullin, which is highly expressed in rat adrenal medulla. ADM and PAMP did not affect either basal or ACTH-stimulated aldosterone secretion of dispersed rat zona glomerulosa cells. In contrast, both peptides markedly suppressed angiotensin-II-stimulated aldosterone production, PAMP being much more effective than ADM (minimal effective concentration, 10(-10) M versus 10(-8) M. IC50, 2.0 +/- 0.17 x 10(-9) M versus 3.1 +/- 0.22 x 10(-8) M; P<0.01. Maximum inhibition, 80% versus 43%, respectively). The inhibitory effect of 10(-7) M ADM was completely reversed by the competitive antagonist of type 1 calcitonin gene-related peptide (CGRP) receptors CGRP(8-37) (10(-6) M), while that of 10(-7) M PAMP did not, thereby suggesting that this last peptide acts through specific receptors. Collectively, these findins may suggest that of the two main preproadrenomedullin derived peptides is PAMP which has probably to be considered a physiologic inhibitor of mineralocorticoid secretion in rats.