NMDA neurotoxicity in murine cortical cell cultures is not attenuated by hemoglobin or inhibition of nitric oxide synthesis.
The role of nitric oxide in N-methyl-D-aspartate (NMDA) neurotoxicity was investigated in murine cortical cell cultures. Exposure of cultures to 300 microM NMDA for 5 min resulted in death of 50-80% of neurons over the subsequent 24 h. This injury was not attenuated by hemoglobin, the nitric oxide synthase (NOS) inhibitors NG monomethyl-L-arginine (MMA) or N omega-nitro-L-arginine (NA), or L-arginine depletion. Hemoglobin and NOS inhibitors consistently prevented the increase in cyclic guanosine monophosphate (cGMP) seen after NMDA exposure. These results suggest that NMDA neurotoxicity in this cell culture system is mediated, at least in part, by mechanisms other than NOS activation.
Blood Research Division, Letterman Army Institute of Research, Presidio of San Francisco, CA 94129.
R F
RF
Regan
K E
KE
Renn
S S
SS
Panter
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology*; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism
D006454:Hemoglobins; D009498:Neurotoxins; D009569:Nitric Oxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate