Proadrenomedullin N-terminal 20 peptide (PAMP), an endogenous anticholinergic peptide: its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla.
In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca(2+)-dependent exocytotic cosecretion of proadrenomedullin N-terminal 20 peptide (PAMP) (EC50 = 50.1 microM) and catecholamines (EC50 = 63.0 microM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP [1-20]NH2 inhibited carbachol-induced 22Na+ influx via nicotinic receptors (IC50 = 2.5 microM in a noncompetitive manner and thereby reduced carbachol-induced 45Ca2+ influx via voltage-dependent Ca2+ channels (IC50 = 1.0 microM) and catecholamine secretion (IC50 = 1.6 microM). It did not alter high K(+)-induced 45Ca2+ influx via voltage-dependent Ca2+ channels or veratridine-induced 22Na+ influx via voltage-dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca(2+)-dependent exocytosis in response to nicotinic receptor stimulation.
Katoh
F
F
Department of Internal Medicine, Miyazaki Medical College, Japan.
Kitamura
K
K
Niina
H
H
Yamamoto
R
R
Washimine
H
H
Kangawa
K
K
Yamamoto
Y
Y
Kobayashi
H
H
Eto
T
T
Wada
A
A
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D053607:Adrenomedullin; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000502:physiology*; D010455:Peptides; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
D002395:Catecholamines; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D053607:Adrenomedullin; D002217:Carbachol; D012964:Sodium; D002118:Calcium