Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na(+) influx, 45Ca(2+) influx and catecholamine secretion in adrenal chromaffin cells.

In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited nicotine-induced 22Na(+) influx via nicotinic receptors (IC(50)=15.5 microM); the suppression by NS-7 was observed in the presence of ouabain, an inhibitor of Na(+),K(+)-ATPase, and was not attenuated upon the washout of NS-7. NS-7 decreased nicotine-induced maximum influx of 22Na(+) without altering the EC(50) value of nicotine. Also, NS-7 diminished nicotine-induced 45Ca(2+) influx via nicotinic receptors and voltage-dependent Ca(2+) channels (IC(50)=14.1 microM) and catecholamine secretion (IC(50)=19.5 microM). These results suggest that NS-7 produces noncompetitive and long-lasting inhibitory effects on neuronal nicotinic receptors in adrenal chromaffin cells, and interferes with the stimulus-secretion coupling.