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

Abstract

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 × 10 −8 M PTX. PTX-induced CA secretion was dependent on both extracellular Na + and Ca 2+. PTX caused increases in [ 22Na] +- and [ 45Ca] 2+-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] 2+-influx and CA secretion. On the other hand, increase in [ 45Ca] 2+-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] 2+-influx was similar to that for PTX-induced CA secretion. The CA secretion and [ 22Na] +- and [ 45Ca] 2+-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, Co 2+, Cd 2+, inhibited both CA secretion and [ 45Ca] 2+-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.