Quisqualic acid-induced neurotoxicity is protected by NMDA and non-NMDA receptor antagonists.
Quisqualic acid-mediated excitotoxicity has been attributed essentially to the activation of non-N-methyl-D-aspartate (non-NMDA) receptors. In the present study we demonstrate the possible involvement of both NMDA and non-NMDA receptors in quisqualic acid-induced toxicity in mouse brain slices, in vitro. Incubation of mouse brain sagittal slices with various concentrations of quisqualic acid resulted in significant increase in the leakage of lactate dehydrogenase and potassium from the slices into the medium. Prior incubation of mouse brain slices with NMDA (MK-801 or AP7) or non-NMDA receptor antagonists (GDEE or quinoxalinediones) protected against quisqualic acid-mediated toxicity. Slices prepared from animals pretreated in vivo with MK-801 (5 mg/kg b.wt.) were also resistant to the toxic effects of quisqualic acid, indicating the possible involvement of NMDA receptors in quisqualic acid toxicity.
Department of Neurochemistry, National Institute of Mental Health and Neuroscience, Bangalore, India.
K S
KS
Pai
V
V
Ravindranath
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D015640:Ion Channel Gating / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051379:Mice; D011188:Potassium / Q000032:analysis; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000633:toxicity*; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000502:physiology; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D011188:Potassium; D011810:Quinoxalines; D016318:Quisqualic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C056723:FG 9041; C031231:2-amino-7-phosphonoheptanoic acid