Beta-DL-methylene-aspartate, an inhibitor of aspartate aminotransferase, potently inhibits L-glutamate uptake into astrocytes.
[3H]Glutamate uptake into astrocytes in primary culture was potently inhibited by the aspartate analogues L- and D-aspartic acid, DL-threo-beta-hydroxy-aspartic acid-beta-hydroxymate (IC50's: 136, 259, 168, and 560 microM, respectively) and by beta-DL-methylene-aspartate, a suicide inhibitor of aspartate aminotransferase (IC50: 524 microM), and by the endogenous sulphur-containing amino acid L-cysteinesulfinic acid (IC50: 114 microM), [3H]Glutamate uptake was not significantly affected by either N-methyl-D-aspartate or DL-homocysteine thiolactone. These results demonstrate that other excitatory amino acids including aspartate and L-cysteinesulfinic acid (but excluding L-homocysteic acid) interact with the glutamate transport system of astrocytes. Inhibition of glutamate uptake may significantly increase the level of neuronal excitability.
Bender
A S
AS
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City 84112.
Woodbury
D M
DM
White
H S
HS
D027322:Amino Acid Transport System X-AG; D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006023:Glycoproteins / Q000378:metabolism; D007700:Kinetics; D051379:Mice
D027322:Amino Acid Transport System X-AG; D005971:Glutamates; D006023:Glycoproteins; D001224:Aspartic Acid; D018698:Glutamic Acid; C036683:beta-methyleneaspartate; D001219:Aspartate Aminotransferases