ATTENUATION OF TRIMETHYLTIN-EVOKED GLUTAMATE (GLU) EFFLUX FROM RAT CORTICAL AND HIPPOCAMPAL SLICES

Trimethyltin (TMT) is a toxic alkyltin that produces neuronal necrosis in the CNS. TMT stimulates the efflux of the excitatory amino acid gl utamate (GLU) from rat cortical slices. This release is concentration dependent, partially calcium dependent, but not inhibited by calcium c hannel blockers or a NMDA antagonist. In the present study the compoun ds furosemide, bumetanide, 4,4'-diisothiocyanatostilbene-2,2'-disulfon ic acid (DIDS), and DL-threo-beta-hydroxyaspartic acid (HAA) were test ed for their ability to attenuate TMT-stimulated GLU efflux from rat c ortical and hippocampal slices. Furosemide (1 mM) reduced the TMT-indu ced GLU efflux in cortical slices and hippocampal slices, but bumetani de (0.1 mM) had no effect on TMT-induced GLU efflux. DIDS (1 mM) demon strated a trend toward decreasing GLU efflux from TMT stimulation in b oth the cortex and hippocampus, but this reduction was not significant . However, DIDS was able to prevent the decrease in intracellular GLU content produced by TMT in both the cortical and hippocampal slices. H AA (1 mM) increased the net GLU efflux in both cortical slices and hip pocampal slices, and produced a significant depletion of the glutamate content of the slices. Taurine efflux was stimulated by TMT treatment but was not blocked by the chloride transport inhibitors. These data suggest that cell swelling induced release of GLU may not be directly involved in TMT-induced GLU efflux, and that TMT does not appear to el icit GLU efflux by a mechanism involving reversal of the GLU transport er. Copyright (C) 1996 Elsevier Science Inc.