Effects of protease inhibitors and calmodulin inhibitors on Ca2+ influx and catecholamine secretion in isolated bovine adrenal medullary cells.

Acetylcholine (ACh) (10(-4) M) induced Ca2+ influx (21.2 nmol/mg cell protein/3 min) and catecholamine (CA) secretion (11.5% of total CA content) in isolated bovine adrenal medullary cells. Both excess K+ (56 mM KCl) and a calcium ionophore (A-23187: 10(-5) M) also induced CA secretion (9.7 and 7.5%, respectively, of total CA content). Protease inhibitors [gabexate mesilate (FOY), TLCK], a synthetic substrate of protease (TAME) and calmodulin inhibitors (W-7, trifluoperazine, promethazine, chlorpromazine) inhibited Ca2+ influx and CA secretion induced by ACh. Protease inhibitors and a substrate of protease had no effect on CA secretion induced by excess K+, and a high concentration of calmodulin inhibitors was required to inhibit excess K+-induced CA secretion. CA secretion induced by A-23187 was not inhibited by these inhibitors and the substrate.