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

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 [() I]PAMP-binding sites in both zona glomerulosa...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 1999-05, Vol.33 (5), p.1185-1189
Main Authors: Belloni, Anna S, Rossi, Gian Paolo, Andreis, Paola G, Aragona, Francesco, Champion, Hunter C, Kadowitz, Philip J, Murphy, William A, Coy, David H, Nussdorfer, Gastone G
Format: Article
Language:English
Subjects:
Adrenal Glands - drug effects
Adrenal Glands - metabolism
Adrenals. Interrenals
Adult
Aldosterone - analysis
Aldosterone - metabolism
Analysis of Variance
Autoradiography
Binding Sites
Biological and medical sciences
Calcium - metabolism
Calcium Channels - metabolism
Chromatography, High Pressure Liquid
Epinephrine - analysis
Epinephrine - metabolism
Fundamental and applied biological sciences. Psychology
Humans
In Vitro Techniques
Middle Aged
Morphology. Functional localizations
Norepinephrine - analysis
Norepinephrine - metabolism
Peptide Fragments - metabolism
Peptide Fragments - physiology
Peptides - metabolism
Peptides - physiology
Potassium - metabolism
Proteins - metabolism
Proteins - physiology
Radioimmunoassay
Receptors, Cell Surface - antagonists & inhibitors
Receptors, Cell Surface - metabolism
Receptors, Cell Surface - physiology
Vertebrates: endocrinology
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Summary: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 [() 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 Ca () 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 Ca, agonist-stimulated aldosterone and catecholamine secretion, acting via specific receptors and through a mechanism involving the impairment of Ca 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. (Hypertension. 1999;33:1185-1189.)
ISSN:0194-911X
1524-4563
DOI:10.1161/01.hyp.33.5.1185