Sensitivity of the binding sites on glutamate transporters to neurotoxic agents.
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.
Killinger
S
S
Department of Anatomy and Histology, University of Sydney, NSW, Australia.
Li
Y
Y
Balcar
V J
VJ
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001345:Autoradiography; D001665:Binding Sites / Q000187:drug effects*; D002712:Chlorides / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017967:Zinc Compounds / Q000494:pharmacology*
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002712:Chlorides; D017967:Zinc Compounds; D000643:Ammonium Chloride; D001224:Aspartic Acid; D008627:Mercuric Chloride; C016837:zinc chloride