Document Detail

Pharmacological and functional characterization of excitatory amino acid mediated cytotoxicity in cerebral cortical neurons.
MedLine Citation:
PMID:  1332807     Owner:  NLM     Status:  MEDLINE    
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.
A Schousboe; A Frandsen; P Krogsgaard-Larsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cell biology and toxicology     Volume:  8     ISSN:  0742-2091     ISO Abbreviation:  Cell Biol. Toxicol.     Publication Date:    1992 Jul-Sep
Date Detail:
Created Date:  1992-12-29     Completed Date:  1992-12-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8506639     Medline TA:  Cell Biol Toxicol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  93-100     Citation Subset:  IM    
Dept. of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen.
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MeSH Terms
Amino Acids / toxicity*
Calcium / metabolism
Cell Survival / drug effects
Cells, Cultured
Cerebral Cortex / cytology,  drug effects*,  physiology
Cyclic GMP / metabolism
Neurons / drug effects*,  physiology
Receptors, Glutamate / drug effects*
Reg. No./Substance:
0/Amino Acids; 0/Receptors, Glutamate; 7440-70-2/Calcium; 7665-99-8/Cyclic GMP

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