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Release and uptake of glutamate as related to excitatoxicity
Rev. bras. biol ; 56(supl.1,pt.1): 165-74, Dec. 1996. ilus, graf
Artigo em Inglês | LILACS | ID: lil-196840
RESUMO
It has been established that neurons exposed to high concentrations of glutamate or other excitatory amino acids degenerate and die. Neuronal damage appears to be due to the activation of different types of glutamate receptors, among which the ionotropic N-methyl-D-aspartate (NMDA) type seems particularly involved, since its channel is permeable to Ca2+ and an increase in the cytoplasmic concentration of this cation promotes a chain of events leading to cell death. The mechanism of such glutamate receptor-mediated neurodegeneration has been defined as excitotoxicity, and several pieces of evidence suggest that this mechanism might contribute to the neuronal death associated with certain neurological disorders, such as ischemia, cerebral trauma and some chronic neurodegenerative diseases. A relevant question is whether the origin of endogenous extracellular glutamate is important for the induction of excitotoxicity. An excess of glutamate release, or a deficiency in its clearance from the synaptic cleft, which depends mainly on its transport by high affinity carriers, are potential sources for the accumulation of extracellular glutamate. In the present article some experimental results from our laboratory, aimed at obtaining information on this question, are reviewed. These experiments include the use of 4-aminopyridine, a convulsant drug that enhances the release of glutamate, and of some inhibitors of glutamate transport, in vivo and in neuronal cell cultures. The results obtained indicate that an increase of endogenous extracellular glutamate due to these procedures is not sufficient to induce neuronal death, at least under the experimental condition used.
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Índice: LILACS (Américas) Assunto principal: Técnicas In Vitro / 4-Aminopiridina / N-Metilaspartato / Ácido Glutâmico / Técnicas de Cultura de Células / Degeneração Neural Idioma: Inglês Revista: Rev. bras. biol Assunto da revista: Biologia Ano de publicação: 1996 Tipo de documento: Artigo

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Índice: LILACS (Américas) Assunto principal: Técnicas In Vitro / 4-Aminopiridina / N-Metilaspartato / Ácido Glutâmico / Técnicas de Cultura de Células / Degeneração Neural Idioma: Inglês Revista: Rev. bras. biol Assunto da revista: Biologia Ano de publicação: 1996 Tipo de documento: Artigo