?-Dl-Methylene-aspartate, an inhibitor of aspartate aminotransferase, potently inhibitsl-glutamate uptake into astrocytes

Abstract

[³H]Glutamate uptake into astrocytes in primary culture was potently inhibited by the aspartate analoguesl- andd-aspartic acid,Dl-threo-β-hydroxy-aspartic acid,l-aspartic acid-β-hydroxymate (IC50's: 136, 259, 168, and 560 μM, respectively) and by β-Dl-methylene-aspartate, a suicide inhibitor of asparate aminotransferase (IC50: 524 μM), and by the endogenous sulphur-containing amino acidl-cysteinesulfinic acid (IC50: 114 μM). [³H]Glutamate uptake was not significantly affected by either N-methyl-d-aspartate orDl-homocysteine thiolactone. These results demonstrate that other excitatory amino acids including aspartate andl-cysteinesulfinic acid (but excludingl-homocysteic acid) interact with the glutamate transport system of astrocytes. Inhibition of glutamate uptake may significantly increase the level of neuronal excitability.