[Catecholamine secretion from adrenal chromaffin cells]

The effect of palytoxin (PTX) on catecholamine (CA) secretion from cultured bovine adrenal chromaffin cells was examined. PTX (greater than 10(-10) M) induced CA secretion concentration-dependently. About 40-50% of the total cellular CA was secreted during a 20 min incubation with 3 x 10(-8) M PTX. PTX caused increases in [22Na](+)- and [45Ca](2+)-influxes into the cells, which were not affected by TTX. PTX-induced CA secretion and [22Na](+)- and [45Ca](2+)-influxes were significantly inhibited by quinidine and aprindine, antiarrhythmic drugs. Ca(2+)-channel blockers such as nifedipine, verapamil, Co2+, and Cd2+ inhibited both CA secretion and [45Ca](2+)-influx induced by PTX. These results indicated that PTX-induced CA secretion was mediated by activation of Na(+)-dependent, TTX-insensitive voltage-dependent Ca(2+)-channels. PTX-induced [22Na](+)-influx was inhibited by amiloride, an inhibitor of the Na(+)-H+ exchange system, suggesting that the Na(+)-H+ exchange mechanism might be involved in PTX-induced [22Na](+)-influx into the cells. The effects of flavonoids on CA secretion from permeabilized adrenal chromaffin cells were examined. CA secretion from the cells in response to a direct Ca2+ challenge was inhibited by quercetin (greater than 10(-5) M) and apigenin (greater than 10(-5) M). These flavonoids also inhibited phorbol ester TPA-induced CA secretion. Therefore, the inhibitory effects of flavonoids on CA secretion were thought to be attributed to their inhibitory effects on PKC.