Evidence that CHP100 neuroblastoma cell death induced by N-methyl-D-aspartate involves L-arginine-nitric oxide pathway activation.
Evidence suggests that nitric oxide (NO) may mediate, at least in part, excitotoxic effects of excessive N-methyl-D-aspartate (NMDA) receptor activation both in vivo and in vitro. In the present experiments, NMDA-induced excitotoxicity has been studied in CHP100 neuroblastoma cell cultures. Application of NMDA (0.25-1.5 mM) produced concentration-dependent cell death. These effects were antagonized by co-application of dizocilpine (MK801), a selective and non-competitive NMDA receptor complex antagonist. Protection from NMDA-induced lethal effects was also afforded by N omega-nitro-L-arginine methyl ester, a potent NO-synthase inhibitor, and by hemoglobin, a NO-trapping agent. In addition, substitution of L-arginine, normally present in the exposure solution with its D-isomer, abolished the cell death induced by the excitotoxin. In conclusion, the present experiments support the suggestion that excitotoxic effects induced by NMDA receptor stimulation involve L-arginine-NO pathway activation.
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001711:Biotransformation; D001932:Brain Neoplasms / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester; D009447:Neuroblastoma / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D014407:Tumor Cells, Cultured
D009569:Nitric Oxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester