Measurement of Glutamate Uptake and Reversed Transport by Rat Synaptosome Transporters(Pharmacology)

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To establish an assay system for evaluation of the uptake and reversed transport of glutamate, we examined the effects of Na^+-concentration and pharmacological agents on the extracellular glutamate concentration ([Glu]_0) in rat cortical synaptosomes in vitro. There was a decrease and increase of the [Glu]_0 at high and low Na^+ concentrations, respectively, in a Ca^<2+>-free medium. The changes in [Glu]_0 in both directions were temperature-sensitive, and reversed at around 30 HIM of Na^+. Dihydrokainate (DHK), a non-transportable inhibitor selective for glial glutamate transporter GLT-1, suppressed the decrease in [Glu]_0, and the reversal of [Glu]_0 change was shifted to about 60 mM Na^+. There was no change in the maximum [Glu]_0 at total Na^+ substitution. Further pharmacological analysis revealed that D-aspartate and DL-threo-β-hydroxy-aspartate (THA), transportable substrates of glutamate transporters, increased the [Glu]_0 in standard media. In contrast, β-phenylglutamic acid, a structural analogue of glutamate, suppressed both the decrease in [Glu]_0 in standard medium and the increase in [Glu]_0 in low Na^+ medium. It is, thus, concluded that both the direction and the amount of [Glu]_0 changes are determined by a balance of the uptake and reversed transport of glutamate, and that this assay system is suitable for evaluation of the effect of this on glutamate transporters.
社団法人日本薬学会の論文
2004-06-01