Effects of mercuric chloride on [3H]dopamine release from rat brain striatal synaptosomes.
Electrophysiological studies employing amphibian neuromuscular preparations have shown that mercuric chloride (HgCl2) in vitro increases both spontaneous and evoked neurotransmitter release. The present study examines the effect of HgCl2 on the release of [3H]dopamine from synaptosomes prepared from mammalian brain tissue. Mercuric chloride (3-10 microM) produces a concentration-dependent increase in spontaneous [3H]dopamine release from "purified" rat striatal synaptosomes, in both the presence and absence of extra-synaptosomal calcium. The effects of HgCl2 on transmitter release from amphibian neuromuscular junction preparations resemble those produced by the Na+, K+-ATPase inhibitor ouabain. Experiments were performed to determine whether the HgCl2 effects on mammalian synaptosomal dopamine release are a consequence of Na+, K+-ATPase inhibition. Na+, K+-ATPase activity in lysed synaptosomal membranes is inhibited by HgCl2 (IC50 = 160 nM). However, mercuric chloride in the presence of 1 mM ouabain still increased [3H]dopamine release. The specific inhibitor of Na+-dependent, high-affinity dopamine transport, RMI81,182 inhibited ouabain-induced [3H]dopamine release whereas it had no effect on HgCl2-induced [3H]dopamine release. These data suggest that augmentation of spontaneous [3H]dopamine release by HgCl2 probably is not mediated by an inhibition of Na+, K+-ATPase and HgCl2 does not act directly on the dopamine transporter.
Hare
M F
MF
Department of Environmental Health, University of Cincinnati College of Medicine, Ohio 45267-0056.
Minnema
D J
DJ
Cooper
G P
GP
Michaelson
I A
IA
D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D008627:Mercuric Chloride; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002122:Calcium Chloride; D004298:Dopamine