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.