Trimethyltin and triethyltin differentially induce spontaneous noradrenaline release from rat hippocampal slices

The environmental contaminants trimethyltin (TMT) and triethyltin (TET) stimulated the spontaneous release of [3H]noradrenaline ([3H]NA) from hippocampal slices in a time- and concentration-dependent manner. TMT was the most potent compound, exhibiting an EC50 value 10-fold lower (3.8 ¿M) than that of TET (39.5 ¿M). Metal-evoked [3H]NA release did not increase in the absence of desipramine and was completely blocked by reserpine preincubation, indicating a vesicular origin of [3H]NA release but not a mechanism involving reversal of the transmitter transporter. The voltage-gated Na+ channel blocker tetrodotoxin (TTX) did not affect metal-evoked [3H]NA release. [3H]NA release elicited by TMT was partially extracellular Ca2+dependent, since it was significantly decreased in a Ca2+-free EGTA- containing medium, whereas TET induced an extracellular Ca2+-independent release of [3H]NA. Neither inhibitors of Ca2+entry through Na+/Ca2+exchanger and voltage-gated calcium channels, nor agents that interfere with Ca2+-mobilization from intracellular stores affected [3H]NA release induced by TMT. TET-evoked [3H]NA release was reduced by ruthenium red, which depletes mitochondrial Ca2+stores, but was not modified by caffeine and thapsigargin, which interfere with Ca2+-mobilization from endoplasmic reticulum. The fact that TET effect was also attenuated by DIDS, an inhibitor of anion exchange, indicates that the effect of TET on spontaneous [3H]NA release may be mediated by intracellular mobilization of Ca2+ from mitochondrial stores through a Cl- dependent mechanism. (C) 2000 Academic Press.