Effects of 2-amino-7-phosphonohepatanoic acid, melatonin or NG-nitro-L-arginine on cyanide or N-methyl-D-aspartate-induced neurotoxicity in rat cortical cells.
When cortical neuronal cells were exposed to potassium cyanide (0.01, 0.05, 0.1, 0.5, or 1.0 mM) or N-methyl-D-aspartate (NMDA: 0.005, 0.01, 0.05, 0.1, or 0.2 mM) for 24 h at 37 degrees C in a 95% air and 5% CO2 environment, lactate dehydrogenase (LDH) efflux into the extracellular fluid from the cortical cells was significantly increased in a concentration dependent manner and morphological changes were observed. The increased LDH efflux and the morphological changes in cortical cells induced by potassium cyanide or NMDA were blocked by co-exposure to 2-amino-7-phosphonoheptanoic acid (AP7: 1.0 mM), a selective antagonist of the NMDA receptor, melatonin (1.0 mM), a potent hydroxyl and peroxyl radical scavenger, or NG-nitro-L-arginine (1.0 mM), an inhibitor of nitric oxide (NO) synthase. These results suggest that activation of NMDA receptor and NO synthase and/or free radical formation may contribute to the development of neurotoxicity induced by cyanide or NMDA.
Yamamoto
H
H
University of Tsukuba, Institute of Community Medicine, Ibaraki, Japan.
Tang
H
H
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005609:Free Radicals; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D011042:Poisons / Q000633:toxicity*; D011190:Potassium Cyanide / Q000633:toxicity*; D051381:Rats
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D011042:Poisons; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D008550:Melatonin; D011190:Potassium Cyanide; C031231:2-amino-7-phosphonoheptanoic acid