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.
Mitrovic
A D
AD
Department of Pharmacology, University of Sydney, NSW, Australia.
Johnston
G A
GA
D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism
D003998:Dicarboxylic Acids; D011759:Pyrrolidines; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D012964:Sodium