Characterization of palytoxin-induced catecholamine secretion from cultured bovine adrenal chromaffin cells. Effects of Na(+)- and Ca(2+)-channel blockers.

The effect of palytoxin (PTX), a potent marine toxin, on catecholamine (CA) secretion from cultured bovine adrenal chromaffin cells was examined. PTX at concentrations of over 10(-10) M induced CA secretion concentration-dependently. About 40-50% of the total cellular CA was secreted during 20-min incubation with 3 x 10(-8) M PTX. PTX-induced CA secretion was dependent on both extracellular Na+ and Ca2+. PTX caused increases in 22Na- and 45Ca-influxes into the cells. Increase in 22Na-influx was observed at concentrations of over 10(-11) M PTX and was maximal at 10(-10) M PTX and then gradually decreased at higher concentrations that induced 45Ca-influx and CA secretion. On the other hand, increase in 45Ca-influx was observed at concentrations of over 10(-10) M PTX and increased with increase in concentration of PTX. This concentration-response curve for PTX-induced 45Ca-influx was similar to that for PTX-induced CA secretion. The CA secretion and 22Na- and 45Ca-influxes induced by PTX were not affected by tetrodotoxin (TTX), but were significantly inhibited by quinidine and aprindine(mexiletine), antiarrythmic drugs known to block Na(+)-channels. Ca(2+)-channel blockers such as nifedipine, verapamil, Co2+, Cd2+, inhibited both CA secretion and 45Ca-influx induced by PTX. These results indicate that PTX-induced CA secretion is mediated by activation of Na(+)-dependent, TTX-insensitive voltage-dependent Ca(2+)-channels, and is inhibited by quinidine and aprindine through their inhibitory effects on the Na(+)- and Ca(2+)-influxes into the cells induced by PTX.