[Contribution of MPTP to studies on the pathogenesis of Parkinson's disease].
Progress in the research on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is reviewed, and the impact given by MPTP to the studies on Parkinson's disease is discussed. Our data on the mechanism of the neuronal degeneration in MPTP-induced experimental parkinsonism are also presented. We studied the effects of the 1-methyl-4-phenylpyridinium ion (MPP+) on mitochondrial respiration. Mitochondria were prepared from mouse brains, and oxygen consumption was measured polarographically. Activity of Complex I was measured after the incubation of the mitochondria with NAD(+)-utilizing substrates in the TCA cycle and ADP. MPP+ significantly inhibited the state 3 respiration supported by glutamate. Amount of ATP synthesized was also significantly reduced by MPP+. Activity of Complex I was significantly inhibited by MPP+. This inhibition was observed with 0.05 mM of MPP+ when intact mitochondria were used. These observations suggest mitochondria as the most probable site of the action for MPP+. It appears to be important to search for endogenous or exogenous toxic substances with similar pharmacological properties as MPTP to elucidate pathogenesis of Parkinson's disease. In addition, studies on mitochondrial functions in Parkinson's disease seem to be also important. Some preliminary data are shown.
Mizuno
Y
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine