Open AccessProadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca 2+ -Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands
Author(s) -
Anna S. Belloni,
Gian Paolo Rossi,
P. G. Andreis,
F Aragona,
Hunter C. Champion,
Philip J. Kadowitz,
William A. Murphy,
David H. Coy,
Gastone G. Nussdorfer
Publication year - 1999
Publication title -
hypertension
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.986
H-Index - 265
eISSN - 1524-4563
pISSN - 0194-911X
DOI - 10.1161/01.hyp.33.5.1185
Subject(s) - zona glomerulosa , adrenal medulla , endocrinology , receptor , medicine , aldosterone , agonist , adrenal gland , catecholamine , secretion , angiotensin ii , biology , chemistry
—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 [125 I]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.