title: Effects of a glutamate uptake inhibitor on glutamate release induced by veratridine and ischemia.
abstract: It has been postulated that a reversal of glutamate reuptake ("uptake reverse") may contribute to glutamate release during cerebral ischemia. We tested this hypothesis by studying the effect of threo-3-hydroxy-DL-aspartic acid (THA), a glutamate uptake inhibitor, on extracellular glutamate accumulation measured by microdialysis during 4-vessel ischemia (20 min). The inhibitory effect of THA on sodium-dependent glutamate uptake was measured in vitro on rat hippocampal slices (Ki = 45 +/- 11 microM). We examined in vivo the effect of THA (400 microM in the dialysis solution) on the extracellular glutamate release from the rat hippocampus, during veratridine depolarization and ischemia. THA decreased the amount of glutamate appearing in the extracellular space during veratridine depolarization (61%). In contrast, the glutamate release induced by ischemia was not affected by THA. We conclude that a reversal of the sodium-dependent uptake contributes to an increase in extracellular glutamate during veratridine depolarization. In contrast, glutamate release occurring during ischemia is not mediated by uptake reverse.
authors.affiliation: Laboratoire de Recherches Cérébrovasculaires, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Héron
authors.forename: V
authors.initials: V
authors.lastname: Springhetti
authors.forename: J
authors.initials: J
authors.lastname: Seylaz
authors.forename: F
authors.initials: F
authors.lastname: Lasbennes
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014701:Veratridine / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014179:Neurotransmitter Uptake Inhibitors; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D014701:Veratridine