Nitric oxide inhibitors attenuate N-methyl-D-aspartate excitotoxicity in rat hippocampal slices.
To investigate whether nitric oxide (NO) plays a role in the neurotoxicity produced by N-methyl-D-aspartate (NMDA) we have examined the effects of NO inhibitors on NMDA-mediated neurodegeneration in the CA1 region of rat hippocampal slices. L-NG-Monomethylarginine, L-NG-nitroarginine and hemoglobin markedly diminished the toxicity produced by activation of NMDA receptors without interfering with NMDA receptor-mediated ion currents or synaptic responses. The neuroprotective effects are reversed by coapplication of L-arginine with the NO synthase inhibitors. These results suggest that activation of the NO system is an important component of the biochemical cascade leading to neurodegeneration produced by NMDA receptors.
Izumi
Y
Y
Department of Psychiatry, Washington University Medical School, St. Louis, MO 63110.
Benz
A M
AM
Clifford
D B
DB
Zorumski
C F
CF
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009410:Nerve Degeneration / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D019323:omega-N-Methylarginine
D006454:Hemoglobins; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D001120:Arginine; D002118:Calcium