title: Aspartate neurotoxicity on cultured cortical neurons.
abstract: L-aspartate neurotoxicity was quantitatively characterized in murine cortical cell cultures. Five-minute exposure to 30 microM-3 mM L-aspartate resulted in concentration-dependent (ED50 about 190 microM) neuronal destruction over the next 10 hr; glia were not injured. D-aspartate and L-aspartate were roughly equipotent neurotoxins. Ion substitution experiments suggested that L-aspartate neurotoxicity is comprised of both acute, sodium-dependent "excitotoxicity" and delayed, calcium-dependent degeneration, with the latter predominant under conditions of brief exposure. Aspartate neurotoxicity could be attenuated by D-2-amino-5-phosphonovalerate (D-APV), dextrorphan, ketamine, and kynurenate, but not by L-glutamate diethyl ester or gamma-D-glutamylaminomethyl sulfonate, consistent with principal involvement of N-methyl-D-aspartate receptors. D-APV and dextrorphan produced different effects on the aspartate concentration-toxicity relation; the former drug was consistent with a competitive and the latter with a noncompetitive mechanism of antagonism.
authors.affiliation: Department of Neurology, Stanford University Medical Center, California 94305.
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
authors.forename: V
authors.initials: V
authors.lastname: Viseskul
authors.forename: M
authors.initials: M
authors.lastname: Amirthanayagam
authors.forename: H
authors.initials: H
authors.lastname: Monyer
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D005333:Fetus; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009498:Neurotoxins
chemical_list: D009498:Neurotoxins; D001224:Aspartic Acid; D007770:L-Lactate Dehydrogenase