| Lack of involvement of glutamate-induced excitotoxicity in MPP+ toxicity in striatal dopaminergic terminals: possible involvement of ascorbate. | |
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MedLine Citation:
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PMID: 9222565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. The present study concerns the possible relationship between glutamate excitotoxicity and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP+) neurotoxicity on striatal dopaminergic terminals. 2. MPP+ neurotoxicity has been studied by means of two MPP+ perfusions separated by 24 h. After the second MPP+ 1 mM perfusion, dopamine extracellular output, measured by microdialysis, was considered to be an index of the dopaminergic neurone damage produced by the first MPP+ 1 mM perfusion. 3. High concentration (10 mM) of glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) stimulated basal release of dopamine and protected against the neurotoxic effect of MPP+. 4. PDC 10 mM perfusion produced an increase in the extracellular output of glutamate and aspartate, and a decrease in that of ascorbate. 5. The protective effect against MPP+ toxicity observed with PDC 10 mM was completely abolished when this glutamate uptake inhibitor was co-perfused with ascorbate 0.5 mM. 6. These results suggest that glutamate-induced neurotoxicity is not involved in MPP+ toxicity. The protective effect found with the glutamate uptake inhibitor could be due to a decrease in extracellular ascorbate levels. |
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Authors:
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E R Matarredona; M Santiago; A Machado; J Cano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 121 ISSN: 0007-1188 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 1997 Jul |
Date Detail:
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Created Date: 1997-09-15 Completed Date: 1997-09-15 Revised Date: 2008-11-20 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1038-44 Citation Subset: IM |
Affiliation:
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Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacía, Sevilla, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Methyl-4-phenylpyridinium
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toxicity* Amino Acids, Essential / toxicity* Animals Ascorbic Acid / metabolism, physiology* Aspartic Acid / metabolism Dicarboxylic Acids / pharmacology Dopamine / metabolism, physiology* Dopamine Agents / toxicity* Extracellular Space / enzymology, metabolism Glutamic Acid / physiology* Immunohistochemistry MPTP Poisoning Male Microdialysis Neostriatum / drug effects*, metabolism Nerve Endings / drug effects* Neurotransmitter Uptake Inhibitors / pharmacology Pyrrolidines / pharmacology Rats Rats, Wistar Tyrosine 3-Monooxygenase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids, Essential; 0/Dicarboxylic Acids; 0/Dopamine Agents; 0/Neurotransmitter Uptake Inhibitors; 0/Pyrrolidines; 48134-75-4/1-Methyl-4-phenylpyridinium; 50-81-7/Ascorbic Acid; 56-84-8/Aspartic Acid; 56-86-0/Glutamic Acid; 99319-03-6/pyrrolidine-2,4-dicarboxylic acid; EC 1.14.16.2/Tyrosine 3-Monooxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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