INHIBITION OF NITRIC-OXIDE FORMATION DOES NOT PROTECT MURINE CORTICAL CELL-CULTURES FROM N-METHYL-D-ASPARTATE NEUROTOXICITY

We examined the role of nitric oxide in N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity in rat and mouse primary cortical cell cultures. In rat and mouse cultures, the NO synthase inhibitor, N(G)-Nitro-L-arginine, blocked cGMP formation but not neuronal cell death following a 5-10 min exposure to 300-500 muM NMDA. N(G)-Monomethyl-L-arginine was also unable to prevent neuronal death. In contrast, the non-competitive NMDA receptor antagonist, dextrorphan, prevented both cGMP formation and cell death. While other data suggest that the synthesis of nitric oxide can mediate NMDA receptor-mediated neurotoxicity, present results suggest that such synthesis is not necessarily required.