Document Detail

Complex I inhibitor effect on the nigral and striatal release of dopamine in the presence and absence of nomifensine.
MedLine Citation:
PMID:  8566093     Owner:  NLM     Status:  MEDLINE    
The effect of inhibitors of complex I respiratory chain--1-methyl-4-phenylpyridinium ion (MPP+, 10 microM) and rotenone (100 microM)--on the release and metabolism of dopamine was studied by in vivo microdialysis in the striatum and substantia nigra. Both compounds produced a marked increase in the release of dopamine in the striatum and substantia nigra, which was diminished when nomifensine (20 microM) was included in the perfusion fluid. The 3,4-dihydroxyphenylacetic acid (DOPAC) extracellular output was decreased under MPP+ (10 microM) perfusion in the striatum and substantia nigra, in the presence and in the absence of nomifensine (20 microM). However, perfusion of rotenone (100 microM) increased or had no effect on DOPAC outflow. Homovanillic acid levels were affected in the same way as DOPAC levels, but the changes were always much less pronounced. These results suggest that the neurotoxic action of MPP+ or rotenone is similar in the striatum and substantia nigra, indicating the importance of the dopamine uptake system in this neurotoxic action of MPP+ or rotenone, also suggesting that the dopamine uptake system could have low selectivity and also transports other substances such as rotenone.
M Santiago; L Granero; A Machado; J Cano
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  280     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1995 Jul 
Date Detail:
Created Date:  1996-03-07     Completed Date:  1996-03-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  251-6     Citation Subset:  IM    
Departamento de Bioquímica, Facultad de Farmacia, Sevilla, Spain.
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MeSH Terms
1-Methyl-4-phenylpyridinium / pharmacology
3,4-Dihydroxyphenylacetic Acid / metabolism
Analysis of Variance
Corpus Striatum / drug effects*,  metabolism
Dopamine / metabolism*
Dopamine Agents / pharmacology*
Dopamine Uptake Inhibitors / pharmacology*
Homovanillic Acid / metabolism
Hydroxyindoleacetic Acid / metabolism
Nomifensine / pharmacology*
Rats, Wistar
Rotenone / pharmacology
Substantia Nigra / drug effects*,  metabolism
Uncoupling Agents / pharmacology
Reg. No./Substance:
0/Dopamine Agents; 0/Dopamine Uptake Inhibitors; 0/Uncoupling Agents; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 24526-64-5/Nomifensine; 306-08-1/Homovanillic Acid; 48134-75-4/1-Methyl-4-phenylpyridinium; 54-16-0/Hydroxyindoleacetic Acid; 83-79-4/Rotenone

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