Interaction of trimethyltin with hippocampal glutamate.
Trimethyltin (TMT) produces selective hippocampal lesions similar to that caused by convulsants which interact with the brain excitatory amino acid transmission. The hippocampal glutamate system was studied because of its possible contribution to neuronal damage produced by TMT. At 24 hr following administration of TMT (3 mg/kg; ip) to mice, hippocampal glutamate levels were decreased, although no changes in levels were observed at 1 hr, 6 hr or 15 hr. In partially depolarized hippocampal slices, TMT (10 microM), produced a release of endogenous glutamate. Continuous monitoring by fluorometry found glutamate release to occur immediately following addition of TMT to partially depolarized slices; this release was dependent on extracellular calcium. These results indicate TMT can activate the endogenous excitotransmitter system, which may contribute to the neuronal damage associated with TMT exposure.
Patel
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M
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
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D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009498:Neurotoxins / Q000633:toxicity*; D011189:Potassium Chloride / Q000494:pharmacology; D012016:Reference Values; D014298:Trimethyltin Compounds / Q000633:toxicity*
D005971:Glutamates; D009498:Neurotoxins; D014298:Trimethyltin Compounds; C046488:trimethyltin; D004533:Egtazic Acid; D011189:Potassium Chloride; D002118:Calcium