BIBP 3226 inhibition of nicotinic receptor mediated chromaffin cell secretion

(R)-N-2-(diphenacetyl)-N-[(4-hydroxypheny)methyl]-arginiamide (BIBP 3226) i s a selective neuropeptide Y Y-1 receptor antagonist with structural simila rity to the C-terminal tripeptide of neuropeptide Y. Based on this similari ty we questioned whether BIBP 3226 could act as an agonist. Incubation of B IBP 3226 with bovine chromaffin cells in culture results in the inhibition of nicotinic receptor-stimulated catecholamine secretion (IC50 = 2.4 mu M). The effect of BIBP 3226 is independent of neuropeptide Y action since the presence of neuropeptide Y in the culture medium does not alter the effect of BIBP 3226. BIBP 3226 decreased the efficacy of the nicotinic receptor ag onist, 1,1-dimethyl-4-phenylpiperizinium (DMPP), but did not change its pot ency suggesting non-competitive inhibition. BIBP 3226 has a similar effect on nicotinic receptor-stimulated Ca-45(2+) influx. BIBP 3226 does not inhib it [H-3]norepinephrine release induced by high K+ and its effect is not per tussis toxin-sensitive. We conclude that not only can BIBP 3226 act as a ne uropeptide Y receptor antagonist in bovine chromaffin cells but also act as an agonist and inhibit catecholamine secretion. (C) 1998 Elsevier Science B.V. All rights reserved.