Effects of SK&F 96365, an inhibitor of receptor-mediated Ca2+ entry, on Ca2+ influx and catecholamine secretion in bovine adrenal chromaffin cells.

SK&F 96365 (1-[3-(4-methoxyphenyl)propoxyl]-1-(4-methoxyphenyl)ethyl-1H- imidazole HCl) (1-50 microM), an inhibitor of receptor-mediated Ca2+ entry, reduced both acetylcholine (ACh)- and 56 mM K+ (high K+)-induced 45Ca2+ influxes and catecholamine secretion in bovine adrenal chromaffin cells. However, SK&F 96365 at lower concentrations (1-3 microM) inhibited only ACh-induced 45Ca2+ influx and secretion but not their high K(+)-induction. In Na(+)-free medium, ACh-induced 45Ca2+ influx and secretion were also considerably decreased by SK&F 96365 at low concentrations (1-3 microM). These results suggest that in the chromaffin cells, not only voltage-sensitive calcium channels but also ACh receptor-operated calcium channels at least in part contribute to the influx of Ca2+ which triggers the catecholamine secretion from the cells when the cells are exposed by ACh.