Inhibition of gamma-[3H]aminobutyric acid uptake by organotin compounds in vitro.
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.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009947:Organotin Compounds / Q000494:pharmacology*; D010042:Ouabain / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013327:Strophanthidin / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009947:Organotin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D010042:Ouabain; D013327:Strophanthidin; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase; C007567:triphenyltin hydroxide