LACK OF INVOLVEMENT OF NITRIC-OXIDE IN NMDA-INDUCED NEURONAL CELL-DEATH IN CORTICAL CULTURE

IN primary cultures of rat cerebral cortex, N-methyl-D-aspartate cause s widespread neurotoxicity. Inhibitors of the nitric oxide generating the enzyme nitric oxide synthase has been shown to attenuate the effec ts of N-methyl-D-aspartate in a number of neuronal systems both in viv o and in vitro. In our experiments, the nitric oxide synthase inhibito r N-nitroarginine was ineffective at blocking neurotoxicity induced by N-methyl-D-aspartate. Cyclic guanine monophosphate, known to be synth esized in response to nitric oxide was demonstrably inhibited by ident ical treatments with N-nitroarginine in sister cultures. We conclude t hat although nitric oxide is produced in response to N-methyl-D-aspart ate, it is neither necessary nor sufficient for neurotoxicity.