Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures: altered uptake and efflux of rubidium, L-glutamate and D-aspartate.
Studies were undertaken to assess the effects of trimethyl tin (TMT) on metabolic functions in primary neonatal rat cultured astrocytes. Concentrations as low as 10(-5) M TMT significantly inhibited the initial rate (1 min) of uptake of 86RbCl, used as a tracer for K+. TMT also markedly inhibited the initial rate (1 min) of Na(+)-dependent uptake of L-[3H]glutamate and D-[3H]aspartate, and stimulated the release of intracellular 86Rb+, -[3H]glutamate and D-[3H]aspartate in a dose-dependent fashion. These observations support the hypothesis that the astrocyte plasma membrane is potentially an important target for TMT's toxic effect and specifically that small concentrations of this organometal can inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, and exacerbate on-going swelling. Increased levels of glutamate and aspartate in the extracellular fluid upon release from astrocytes may play an important role in TMT neurotoxicity.
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
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Aschner
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Gannon
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Kimelberg
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism*; D014298:Trimethyltin Compounds / Q000633:toxicity*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D005971:Glutamates; D014298:Trimethyltin Compounds; D001224:Aspartic Acid; D018698:Glutamic Acid; D012413:Rubidium