Document Detail


Lack of involvement of glutamate-induced excitotoxicity in MPP+ toxicity in striatal dopaminergic terminals: possible involvement of ascorbate.
MedLine Citation:
PMID:  9222565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
E R Matarredona; M Santiago; A Machado; J Cano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  121     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-09-15     Completed Date:  1997-09-15     Revised Date:  2008-11-20    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1038-44     Citation Subset:  IM    
Affiliation:
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacía, Sevilla, Spain.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenylpyridinium / 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:
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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