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 [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.
Belloni
A S
AS
Departments of Anatomy, Clinical and Experimental Medicine, School of Medicine, University of Padova, Italy.
Rossi
G P
GP
Andreis
P G
PG
Aragona
F
F
Champion
H C
HC
Kadowitz
P J
PJ
Murphy
W A
WA
Coy
D H
DH
Nussdorfer
G G
GG
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000450:Aldosterone / Q000032:analysis / Q000378:metabolism; D000704:Analysis of Variance; D001345:Autoradiography; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004837:Epinephrine / Q000032:analysis / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D015220:Calcium Channels; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D011956:Receptors, Cell Surface; D000450:Aldosterone; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine