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Hypertension. 1999;33:1185-1189

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(Hypertension. 1999;33:1185-1189.)
© 1999 American Heart Association, Inc.


Scientific Contributions

Proadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca2+-Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands

Anna S. Belloni; Gian Paolo Rossi; Paola G. Andreis; Francesco Aragona; Hunter C. Champion; Philip J. Kadowitz; William A. Murphy; David H. Coy; Gastone G. Nussdorfer

From the Departments of Anatomy (A.S.B., P.G.A., G.G.N.), Clinical and Experimental Medicine (G.P.R.), and Urology (F.A.), School of Medicine, University of Padua, Padua, Italy; and the Departments of Pharmacology (H.C.C., P.J.K.) and Medicine (W.A.M., D.H.C.), School of Medicine, Tulane University, New Orleans, La.

Correspondence to Professor Gastone G. Nussdorfer, Department of Anatomy, Via Gabelli 65, I-35121 Padova, Italy. E-mail ggnanat{at}ipdunidx.unipd.it

Abstract—Proadrenomedullin N-terminal 20 peptide (PAMP) is a 20–amino acid hypotensive peptide expressed in the adrenal medulla. We investigated the localization and function of PAMP receptors in the human adrenal gland. Autoradiography showed the presence of [125I]PAMP-binding sites in both zona glomerulosa and adrenal medulla that were displaced by cold PAMP and PAMP(12–20) but not by other preproadrenomedullin-derived peptides. PAMP, but not PAMP(12–20), counteracted, in a concentration dependent manner, both aldosterone response of zona glomerulosa cells and catecholamine response of adrenal medulla cells to BAYK-8644, the selective agonist of voltage-activated Ca2+ channels, as well as to K+ and angiotensin II. PAMP(12–20) partially reversed this antisecretagogue effect of PAMP. Collectively, these findings suggest (1) that PAMP inhibits Ca2+-dependent, agonist-stimulated aldosterone and catecholamine secretion, acting via specific receptors and through a mechanism involving the impairment of Ca2+ influx; and (2) that PAMP(12–20) acts as a weak antagonist of PAMP receptors, thereby suggesting that both C- and N-terminal sequences of the PAMP molecule are required for this peptide to exert its antisecretagogue action on the human adrenal gland.


Key Words: PAMP • adrenal glands • aldosterone • catecholamines




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