Complex I inhibitor effect on the nigral and striatal release of dopamine in the presence and absence of nomifensine.
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.
Santiago
M
M
Departamento de Bioquímica, Facultad de Farmacia, Sevilla, Spain.
Granero
L
L
Machado
A
A
Cano
J
J
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009627:Nomifensine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D014475:Uncoupling Agents; D012402:Rotenone; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D006897:Hydroxyindoleacetic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid