Sensitivity of the binding sites on glutamate transporters to neurotoxic agents

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Autoradiography of [3H]L-aspartate binding to sections of rat brain was used to study the sensitivity of Na(+)-dependent glutamate transporters to neurotoxic agents such as Zn2+, NH4+, oxygen-containing free radicals and mercuric chloride. Only mercuric chloride was a strong inhibitor in cerebral neocortex, hippocampus, neostriatum, thalamus and cerebellar cortex. It is concluded that the substrate-binding sites on Na(+)-dependent glutamate transporters are relatively resistant to direct effects of Zn2+, NH4+ and free radicals but they may depend on the structural integrity of thiol bonds. Direct inhibitory effect of mercury on the binding site could significantly contribute to its long-term neurotoxicity.