Inhibitory effect of okadaic acid on carbachol-evoked secretion of catecholamines in cultured bovine adrenal medullary cells.
We examined the effect of okadaic acid on catecholamine secretion caused by carbachol in cultured bovine adrenal medullary cells. Treatment of cells with 100 nM okadaic acid for 3-24 hr produced an inhibition of catecholamine secretion stimulated by carbachol. The half-maximal and maximal inhibition of secretion was observed at 40 nM and 300 nM okadaic acid for 24 hr, respectively. Okadaic acid also inhibited veratridine- and high K(+)-induced secretion but not ionomycin-induced secretion. Okadaic acid strongly suppressed 45Ca2+ influx and slightly inhibited 22Na+ influx in carbachol-stimulated cells. These results suggest that okadaic acid inhibits carbachol-evoked secretion of catecholamines mainly by suppression of Ca2+ influx in adrenal medullary cells.