Absence of implication of L-arginine/nitric oxide pathway on neuronal cell injury induced by L-glutamate or hypoxia.
L-glutamate, N-methyl-D-aspartate (NMDA), kainate, quisqualate and sodium nitroprusside increased cyclic GMP (cGMP) level on rat whole brain cell culture. The accumulation of cGMP evoked by L-glutamate was inhibited by a NMDA antagonist MK-801, an inhibitor of guanylate cyclase methylene blue and two nitric oxide (NO) synthase inhibitors NG-monomethyl-L-arginine (L-NMMA) and L-NG-nitroarginine (NO2Arg). The inhibition of L-NMMA on cGMP level was reversed partially by addition of L-arginine. Although MK-801 was able to protect cells from neuronal injury induced by L-glutamate or by 5 h hypoxia, L-NMMA and NO2Arg were ineffective. The present study suggests that cGMP elevation mediated by NO following activation by L-glutamate is not involved in neuronal cell injury.
Demerlé-Pallardy
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C
Institut Henri Beaufour Research Labs., Les Ulis, France.
Lonchampt
M O
MO
Chabrier
P E
PE
Braquet
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P
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000166:cytology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005333:Fetus; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D019323:omega-N-Methylarginine
D005971:Glutamates; D009599:Nitroprusside; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D016318:Quisqualic Acid; D001120:Arginine; D006152:Cyclic GMP; D007608:Kainic Acid; D015056:1-Methyl-3-isobutylxanthine