Mechanism of the 3H-Norepinephrine Release Induced by Palytoxin from a Rat Pheochromocytoma Cell Line.

Abstract

Palytoxin (PTX), isolated from zoanthid Palytoha sp., is one of the most potent marine toxins. The mode of norepinephrine (NE) releasing action of PTX was investigated using a rat pheochromocytoma cell line (PC12). PTX caused a dose-dependent release of 3H-NE from PCl2. This release was markedly inhibited by Co2+ or Ca2+-free medium, but was not affected by tetrodotoxin (TTX). The release of 3H-NE induced by a low dose (3×10−8M) of PTX was abolished in Na-free medium and increased as external Na+ was raised from 3 to 100 mM, but the NE release by a high dose (10−6 M) was not affected by varying the concentrations of Na+ from 0 to 100 mM. The release of 3H-NE induced by both doses of PTX increased with increasing external Ca2+ from 0 to 3 mM. PTX caused a dose-dependent increase in 22Na and 45Ca influx into PCl2 cells at concentration of 10−10 - 10−8 M and 10−9 - 10−6 M, respectively. The PTX-induced 45Ca influx was markedly inhibited by Co2+, while the PTX-induced 22Na influx was not affected by TTX. These results suggest that the NE release induced by lower doses of PTX is primarily brought about by increasing TTX-insensitive Na+ permeability across the cell membrane of PCl2 cells, whereas that by higher doses is mainly due to a direct increase in Ca influx into them.