Mechanism of palytoxin-induced [3H]norepinephrine release from a rat pheochromocytoma cell line.

Palytoxin, isolated from the zoanthid Palytoha species, is one of the most potent marine toxins. Palytoxin (1 nM-1 microM) caused a release of [3H]norepinephrine from clonal rat pheochromocytoma cells in a concentration-dependent manner. This releasing action of palytoxin was markedly inhibited or abolished by Co2+ or Ca2+ -free medium, but was not modified by tetrodotoxin. The release of [3H]norepinephrine induced by a low concentration (30 nM) of palytoxin was abolished in sodium-free medium and increased as the external Na+ concentrations were increased from 3 to 100 nM, but the release induced by a high concentration (1 microM) was unaffected by varying the concentration of external Na+ from 0 to 100 mM. The release of [3H]norepinephrine induced by both concentrations of palytoxin increased with increasing Ca2+ concentrations from 0 to 3 mM. Palytoxin caused a concentration-dependent increase in 22Na and 45Ca influxes into pheochromocytoma cells at concentrations of 0.1 nM-10 nM and 1 nM-1 microM, respectively. The palytoxin-induced 45Ca influx was markedly inhibited by Co2+, whereas the palytoxin-induced 22Na influx was not affected by tetrodotoxin. These results suggest that in pheochromocytoma cells the [3H]norepinephrine release induced by lower concentrations of palytoxin is primarily brought about by increasing tetrodotoxin-insensitive Na+ permeability across the cell membrane, whereas that induced by higher concentrations is mainly caused by a direct increase in Ca2+ influx into them.