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Toxicology and applied pharmacology

Inhibition of gamma-[3H]aminobutyric acid uptake by organotin compounds in vitro.


PMID 2994257

Abstract

Trimethyltin, 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 gamma-[3H]aminobutyric acid (GABA) into mouse forebrain synaptosomes in vitro. All organotins containing three carbon-tin bonds were potent inhibitors of [3H]GABA uptake with IC50 values ranging from 10(-4) to 10(-6) M. 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.

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