Regional Heterogeneity of L‐Glutamate and L‐Aspartate High‐Affinity Uptake Systems in the Rat CNS

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Abstract
The high‐affinity uptake of L‐[3H]glutamate and L‐[3H]aspartate into synaptosomes prepared from rat cerebral cortical, hippocampal, and cerebellar tissue was reduced by a number of structural analogues of L‐glutamate and L‐aspartate. thero‐3‐Hydroxy‐L‐aspartic acid was a more potent inhibitor of L‐glutamate uptake than of L‐aspartate uptake in the cerebral cortex, but not in the hippocampus or cerebellum. A similar pattern of selectivity was observed for cis‐l‐aminocyclobutane‐1,3‐dicarboxylic acid. Dihydrokainate was also more potent against L‐glutamate than against L‐aspartate in the cerebral cortex, but in the hippocampus, it was more potent against L‐aspartate than against L‐glutamate. By contrast, L‐α‐aminoadipate was significantly more potent in the cerebellum than in the cerebral cortex and hippocampus as an antagonist of both L‐glutamate and L‐aspartate. These results support other evidence that there is regional heterogeneity in acidic amino acid uptake sites and that the amino acids L‐glutamate and L‐aspartate may be taken up by a number of transport systems with overlapping substrate specificity but different inhibitor profiles.

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