N-METHYL-D-ASPARTATE RECEPTORS MEDIATE CYANIDE-INDUCED CYTOTOXICITY IN HIPPOCAMPAL CULTURES

We reported previously that glutamate excitotoxicity may contribute to cyanide-induced neuronal injury. Cyanide stimulates glutamate release which can activate glutamate receptors to initiate excitotoxic proces ses. This study examines the role of EAA receptor subtypes in mediatin g cyanide-induced cytotoxicity. Cytotoxicity was assessed in primary r at hippocampal cultures by measuring lactate dehydrogenase (LDH) in th e culture media. NaCN (0.1 - 10 mM) or glutamate (0.01 - 1 mM) produce d concentration-dependent cytotoxicity following 18 hrs of incubation. Glutamate-induced cytotoxicity was partially blocked by the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA a ntagonist, 2-amino-5-phosphonovalerate (APV). Simultaneous exposure of cultures to both CNQX and APV provided complete protection against gl utamate cytotoxicity. NaCN-induced cytotoxicity was not blocked by CNQ X, but completely blocked by APV and simultaneous exposure to CNQX and APV did not offer added protection. These results indicate that in hi ppocampal cultures, both non-NMDA and NMDA receptors mediate glutamate excitotoxicity, whereas NaCN-induced cytotoxicity is mediated primari ly by activation of the NMDA receptors. (C) 1993 Intox Press, Inc.