Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells

We studied whether a novel proadrenomedullin derived peptide was present an d what was its physiological function in cultured bovine adrenal chromaffin cells. We found a high level of proadrenomedullin N-terminal I? peptide (P AMP-12) which consists of a peptide from 9th amino acid to 20th amino acid of proadrenomedullin N-terminal 20 peptide (PAMP-20). PAMP-12 was released from the cells along with catecholamine upon stimulation of nicotinic choli nergic receptors. When PAMP-12 was added in the incubation medium, this pep tide inhibited nicotinic receptor-mediated catecholamine release and influx of Na+ and Ca2+ into the cells. PAMP-12 did not affect catecholamine relea se evoked by histamine or by depolarization by high concentration of potass ium. PAMP- 12 also inhibited synthesis of catecholamines as well as the act ivation of tyrosine hydroxylase by nicotinic stimulation. Thus, PAMP-12 is an endogenous peptide that regulates release and synthesis of catecholamine s by acting on nicotinic cholinergic receptors in an autocrine manner in ad renal chromaffin cells. (C) 2001 Elsevier Science B.V. All rights reserved.