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 glutamate (GLU) from rat cortical slices. This release is concentration dependent, partially calcium dependent, but not inhibited by calcium channel blockers or a NMDA antagonist. In the present study the compounds furosemide, bumetanide, 4,4'-diisothiocy-anatostilbene-2,2'-disulfonic acid (DIDS), and DL-threo-beta-hydroxyaspartic acid (HAA) were tested for their ability to attenuate TMT-stimulated GLU efflux from rat cortical and hippocampal slices. Furosemide (1 mM) reduced the TMT-induced GLU efflux in cortical slices and hippocampal slices, but bumetanide (0.1 mM) had no effect on TMT-induced GLU efflux. DIDS (1 mM) demonstrated a trend toward decreasing GLU efflux from TMT stimulation in both 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. HAA (1 mM) increased the net GLU efflux in both cortical slices and hippocampal 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 elicit GLU efflux by a mechanism involving reversal of the GLU transporter.
Patterson
T A
TA
Department of Pharmacodynamics, College of Pharmacy, University of Florida, JHMHC, Gainesville 32610, USA.
Eppler
B
B
Dawson
R
R
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*
D009498:Neurotoxins; D014298:Trimethyltin Compounds; D002034:Bumetanide; C046488:trimethyltin; C011274:3-hydroxyaspartic acid; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005665:Furosemide; D019256:Cadmium Chloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid