| Pharmacological and functional characterization of excitatory amino acid mediated cytotoxicity in cerebral cortical neurons. | |
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MedLine Citation:
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PMID: 1332807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cytotoxic action of the excitatory amino acids (EAAs) glutamate, N-methyl-D-aspartate (NMDA), quisqualate (QA), kainate (KA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA) was studied in cerebral cortical neurons in culture. The pharmacological profile of these actions was characterized using the NMDA selective antagonist D-(-)-2-amino-5-phosphonopentanoate (APV) and the non-NMDA selective antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX), 2-amino-3[3-(carboxymethoxy)-5-methylisoxazol-4-yl]-propionate (AMOA) and 2-amino-3-[2-(3-hydroxy-5-methylisoxazol-4-yl)methyl-5-methyl-3- oxoisoxazolin-4-yl]propionate (AMNH). The role of intracellular Ca++ homeostasis and cGMP production for development of EAA mediated cytotoxicity was assessed by measurements of changes in [Ca++]i using the fluorescent Ca++ chelator Fluo-3 and in cGMP concentrations using a conventional radioimmune assay. It was found that glutamate toxicity involves both NMDA and non-NMDA receptor activation and that aberrations in Ca++ homeostasis brought about by Ca++ influx and/or liberation of Ca++ from internal stores are important for development of toxicity. The drug dantrolene which prevents release of Ca++ from such stores can prevent toxicity induced by glutamate, NMDA and QA completely but has no effect on KA and AMPA toxicity. Changes in cGMP levels appear to play a role for development of glutamate, NMDA and KA toxicity but does not seem to be involved in that triggered by QA and AMPA. |
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Authors:
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A Schousboe; A Frandsen; P Krogsgaard-Larsen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Cell biology and toxicology Volume: 8 ISSN: 0742-2091 ISO Abbreviation: Cell Biol. Toxicol. Publication Date: 1992 Jul-Sep |
Date Detail:
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Created Date: 1992-12-29 Completed Date: 1992-12-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8506639 Medline TA: Cell Biol Toxicol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 93-100 Citation Subset: IM |
Affiliation:
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Dept. of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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toxicity* Animals Calcium / metabolism Cell Survival / drug effects Cells, Cultured Cerebral Cortex / cytology, drug effects*, physiology Cyclic GMP / metabolism Mice Neurons / drug effects*, physiology Receptors, Glutamate / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Receptors, Glutamate; 7440-70-2/Calcium; 7665-99-8/Cyclic GMP |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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