Development of regulatory molecules for EAATs (excitatory amino acid transporters)

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L-Glutamate is the major excitatory neurotransmitter. Termination of glutamate function is mainly achieved by glutamate transporters (EAATs1-5). To identify the physiological roles of EAATs, selective inhibitors are strongly required. We developed the binding assay system to characterize inhibitors for all subtypes of EAATs. We synthesized a tritium derivative of (2S,3S)-3-{3-[4-ethylbenzoylamino]benzyloxy}aspartate ([^3H]ETB-TBOA). As expected, [^3H]ETB-TBOA showed significant specific binding to EAATs. The binding was Na^+-dependent and was displaced by known substrates and blockers. The rank order of the inhibition by these compounds was well consistent with the reported results in the uptake assay. Thus, the binding assay using [^3H]ETB-TBOA would be useful to screening novel inhibitors for all subtypes of EAATs.