NMDA Receptor antagonists prevent acute ammonia toxicity in mice
| Autor: | Goizane Marcaida, Santiago Grisolia, Vicente Felipo, Carmina Montoliu, Carlos Hermenegildo, María-Dolores Miñana |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Time Factors Free Radicals Neurotoxins Glutamic Acid Mice Inbred Strains Kainate receptor AMPA receptor Pharmacology Receptors N-Methyl-D-Aspartate Biochemistry Mice Cellular and Molecular Neuroscience Ammonia Muscarinic acetylcholine receptor Phosphoprotein Phosphatases medicine Animals Phencyclidine Neurons Cell Death GABAA receptor Chemistry Calcineurin Glutamate receptor General Medicine Enzyme Activation Neuroprotective Agents Nicotinic agonist nervous system NMDA receptor Calmodulin-Binding Proteins Nitric Oxide Synthase Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Neurochemical Research. 21:1237-1244 |
| ISSN: | 1573-6903 0364-3190 |
| DOI: | 10.1007/bf02532401 |
| Popis: | We proposed that acute ammonia toxicity is mediated by activation of NMDA receptors. To confirm this hypothesis we have tested whether different NMDA receptor antagonists, acting on different sites of NMDA receptors, prevent death of mice induced by injection of 14 mmol/Kg of ammonium acetate, a dose that induces death of 95% of mice. MK-801, phencyclidine and ketamine, which block the ion channel of NMDA receptors, prevent death of at least 75% of mice. CPP, AP-5, CGS 19755, and CGP 40116, competitive antagonists acting on the binding site for NMDA, also prevent death of at least 75% of mice. Butanol, ethanol and methanol which block NMDA receptors, also prevent death of mice. There is an excellent correlation between the EC50 for preventing ammonia-induced death and the IC50 for inhibiting NMDA-induced currents. Acute ammonia toxicity is not prevented by antagonists of kainate/AMPA receptors, of muscarinic or nicotinic acetylcholine receptors or of GABA receptors. Inhibitors of nitric oxide synthase afford partial protection against ammonia toxicity while inhibitors of calcineurin, of glutamine synthetase or antioxidants did not prevent ammonia-induced death of mice. These results strongly support the idea that acute ammonia toxicity is mediated by activation of NMDA receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink