Delayed production of nitric oxide contributes to NMDA-mediated neuronal damage.
Exposure of primary murine cortical neuron cultures to N-methyl-D-aspartate (NMDA) resulted in neuronal death as evidenced by release of lactate dehydrogenase (LDH) into the media. The addition of N-nitro-L-arginine (N-Arg) protected the neurons from death in a concentration-dependent manner when added after the NMDA, but not when the N-Arg was present with the NMDA. Protection by N-Arg was lost if L-arginine containing media was added to the cultures prior to the addition of the N-Arg. Treatment of the neurons with kainate prior to NMDA reduced subsequent NMDA-induced damage which was not prevented with N-Arg. These results suggest that delayed production of nitric oxide (NO) contributes to NMDA-induced neuronal damage in culture.
Biology Department, Fisons Pharmaceuticals, Rochester, NY 14603.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine
D019335:Nitroarginine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D001120:Arginine; D007770:L-Lactate Dehydrogenase