6,7-Dinitroquinoxaline-2,3-dione blocks the cytotoxicity of N-methyl-D-aspartate and kainate, but not quisqualate, in cortical cultures
| Autor: | William C. Zinkand, Andre I. Salama, Thomas J. Mangano, Richard A. Keith, Jitendra Patel, Andrea B. Klika |
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| Rok vydání: | 1990 |
| Předmět: |
N-Methylaspartate
Cell Survival Neurotoxins Kainate receptor Quinoxalinedione Pharmacology Biology Ligands Biochemistry Hippocampus Receptors N-Methyl-D-Aspartate Cellular and Molecular Neuroscience chemistry.chemical_compound Norepinephrine Quinoxalines medicine DNQX Neurotoxin Animals Neurotransmitter Cells Cultured Cerebral Cortex Aspartic Acid Oxadiazoles Kainic Acid Neurotoxicity Glutamate receptor Quisqualic Acid medicine.disease Receptors Neurotransmitter chemistry NMDA receptor |
| Zdroj: | Journal of neurochemistry. 55(1) |
| ISSN: | 0022-3042 |
| Popis: | Based on radioligand binding and electrophysiological studies, quinoxalinediones such as 6,7-dinitroquinoxaline-2,3-dione (DNQX) have been shown to be potent competitive antagonists at the quisqualate and kainate subtypes of the glutamate receptor. In this report we have examined the effects of DNQX on excitatory amino acid neurotoxicity and evoked neurotransmitter release. DNQX was found to be a potent neuroprotective agent against glutamate and N-methyl-D-aspartate (NMDA) neurotoxicity. The data suggest that this neuroprotective activity of DNQX is due to its antagonism of the coagonist activity of glycine at the NMDA receptor–channel complex. The specificity of DNQX for the glycine site associated with the NMDA receptor–channel complex was confirmed in radioligand binding and neurotransmitter release studies. DNQX also prevented kainate neurotoxicity and kainate-evoked neurotransmitter release, presumably by direct competition for the kainate receptor. DNQX, however, did not prevent quisqualate neurotoxicity, suggesting that a novel quisqualate-preferring receptor insensitive to DNQX may mediate quisqualate toxicity. |
| Databáze: | OpenAIRE |
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