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EnglishTrimethyltin, its tetra-, di-, and monomethyl analogs, inorganic tin (Sn II and Sn IV), triethyltin, tripropyltin, tributyltin, and triphenyltin were tested for their ability in inhibiting the uptake of γ-[3H]aminobutyric acid (GABA) into mouse forebrain synaptosomes in vitro. All organotins containing three carbontin bonds were potent inhibitors of [3H]GABA uptake with IC50 values ranging from 10-4 to 10-6m. Various thiol and sulfur compounds, particularly sodium sulfide, were capable of antagonizing the inhibitory effect of triphenyltin and, to a minor extent, of other organotins. All triorganotins also inhibited Na+,K+-ATPase, measured by binding of [3H]ouabain and by hydrolysis of ATP. Although a correlation between inhibition of ouabain binding and GABA uptake by organotins could be found, inhibition of [3H]GABA uptake by the specific inhibitors ouabain and strophantidin was qualitatively and quantitatively different from organotins. These results suggest that all triorganotins are capable of inhibiting synaptosomal [3H]GABA uptake in vitro by a mechanism involving, but not exclusively, inhibition of Na+,K+-ATPase. The role of [3H]GABA uptake inhibition in the neurotoxicity of organotins remains to be determined. © 1985.
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