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 r eceptors by carbachol evoked the Ca2+-dependent exocytotic cosecretion of proadrenomedullin N-terminal 20 peptide (PAMP) (EC(50) = 50.1 mu M ) and catecholamines (EC(50) = 63.0 mu M), with the molar ratio of PAM P/catecholamines secreted being equal to the ratio in the cells. Addit ion of PAMP [1-20] NH, inhibited carbachol-induced Na-22(+) influx via nicotinic receptors (IC50 = 2.5 mu M) in a noncompetitive manner and thereby reduced carbachol-induced Ca-45(2+) influx via voltage-depende nt Ca2+ channels (IC50 = 1.0 mu M) and catecholamine secretion (IC50 = 1.6 mu M). It did not alter high K+-induced Ca-45(2+) influx via volt age-dependent Ca2+ channels or veratridine-induced Na-22(+) influx via voltage-dependent Na+ channels. PAMP seems to be a novel antinicotini c peptide cosecreted with catecholamines by a Ca2+-dependent exocytosi s in response to nicotinic receptor stimulation.