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Comparison of effects of DL-threo-beta-benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of [3h]D-aspartate in astrocytes and glutamatergic neurons.
Waagepetersen, H S; Shimamoto, K; Schousboe, A.
Afiliación
  • Waagepetersen HS; NeuroScience PharmaBiotec Res Center, Dept of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen.
Neurochem Res ; 26(6): 661-6, 2001 Jun.
Article en En | MEDLINE | ID: mdl-11519725
Uptake and release processes in cerebellar astrocytes and granule neurons (glutamatergic) for glutamate were investigated by the use of [3H]D-aspartate, a non-metabolizable glutamate analog. The effects of DL-threo-beta-benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of [3H]D-aspartate were studied. Both compounds inhibited potently uptake of [3H]D-aspartate in neurons and astrocytes (IC50 values 10-100 microM), DL-TBOA being slightly more potent than t-2,4-PDC. Release of preloaded [3H]D-aspartate from neurons or astrocytes could be stimulated by addition of excess t-2,4-PDC whereas addition of DL-TBOA had no effect on [3H]D-aspartate efflux. Moreover, DL-TBOA inhibited significantly the depolarization-induced (55 mM KCI) release of preloaded [3H]D-aspartate in the neurons. The results reflect the fact that DL-TBOA is not transported by the glutamate carriers while t-2,4-PDC is a substrate which may heteroexchange with [3H]D-aspartate. It is suggested that DL-TBOA may be used to selectively inhibit depolarization coupled glutamate release mediated by reversal of the carriers.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirrolidinas / Astrocitos / Inhibidores de la Captación de Neurotransmisores / Ácido Glutámico / Ácido D-Aspártico / Ácidos Dicarboxílicos / Neuronas Límite: Animals Idioma: En Revista: Neurochem Res Año: 2001 Tipo del documento: Article Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirrolidinas / Astrocitos / Inhibidores de la Captación de Neurotransmisores / Ácido Glutámico / Ácido D-Aspártico / Ácidos Dicarboxílicos / Neuronas Límite: Animals Idioma: En Revista: Neurochem Res Año: 2001 Tipo del documento: Article Pais de publicación: Estados Unidos