Regional heterogeneity of L-glutamate and L-aspartate high-affinity uptake systems in the rat CNS.
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. threo-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-1-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-alpha-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.
Fletcher
E J
EJ
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Johnston
G A
GA
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism* / Q000502:physiology; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D005971:Glutamates / Q000378:metabolism / Q000493:pharmacokinetics*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D005971:Glutamates; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid