Regional differences in the inhibition of L-glutamate and L-aspartate sodium-dependent high affinity uptake systems in rat CNS synaptosomes by L-trans-pyrrolidine-2,4-dicarboxylate, threo-3-hydroxy-D-aspartate and D-aspartate.

The sodium-dependent high affinity transport of L-[3H]glutamate and L-[3H]aspartate into synaptosomal fractions prepared from three different regions was employed to investigate the inhibitors L-trans-pyrrolidine-2,4-dicarboxylate, threo-3-hydroxy-D-aspartate and D-aspartate. These substances showed regional heterogeneity as inhibitors of sodium-dependent high affinity uptake of L-glutamate and L-aspartate. L-trans-Pyrrolidine-2,4-dicarboxylate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate in the cortex (IC50 8 microM vs L-glutamate and 13 microM vs L-aspartate) and cerebellum (IC50 4 microM v L-glutamate and 8 microM vs L-aspartate). threo-3-Hydroxy-D-aspartate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate in the cortex (IC50 9 microM vs L-glutamate and 13 microM vs L-aspartate) and hippocampus (IC50 6 microM v L-glutamate and 11 microM v L-aspartate). D-Aspartate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate only in the cortex (IC50 8 microM vs L-glutamate and 15 microM vs L-aspartate). These results thus support other evidence that there is regional heterogeneity in sodium-dependent high affinity acidic amino acid uptake sites in the brain.