Pharmacological characterization of the effects of methylmercury and mercuric chloride on spontaneous noradrenaline release from rat hippocampal slices

The environmental contaminants methylmercury (MeHg) and mercuric chloride (HgCl 2) stimulated the spontaneous release of [ 3H]noradrenaline ([ 3H]NA) from hippocampal slices in a time- and concentration-dependent manner. Both MeHg and HgCl 2 were similarly potent, with an EC 50 of 88.4 μM and 75.9 μM, respectively. The releasing effects of MeHg and HgCl 2 increased in the presence of desipramine, showing that the mechanism does not involve reversal of the transmitter transporter, and were completely blocked by reserpine preincubation, indicating a vesicular origin of [ 3H]NA release. The voltage-gated Na + channel blocker tetrodotoxin (TTX) did not affect the response to mercury compounds. [ 3H]NA release elicited by MeHg was partially dependent on extracellular Ca 2+, since it decreased significantly in a Ca 2+-free EGTA-containing medium whereas HgCl 2 induced a release of [ 3H]NA independent of extracellular Ca 2+. Neither Ca 2+-channels blockers, cobalt chloride (CoCl 2) and ω-conotoxin-GVIA, nor the Na +/Ca 2+-exchanger inhibitor benzamil reduced MeHg-evoked [ 3H]NA release. Moreover, thapsigargin or caffeine, endoplasmic reticulum Ca 2+-depletors, did not modify metal-evoked [ 3H]NA release, whereas ruthenium red, which inhibits the mitochondrial Ca 2+ transport, decreased the effect of both MeHg and HgCl 2. All these data indicate that, in hippocampal slices, mercury compounds release [ 3H]NA from the vesicular pool by a mechanism involving Ca 2+ mobilization from mitochondrial stores.