1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite cyperquat (MPP+) and energy transduction in mitochondria from rat striatum and liver.
In vitro studies with rat striatal and liver mitochondria have shown that the neurotoxic compound MPTP (0.5 mM) has very little effect on mitochondrial energy transduction. With pyruvate-malate (P/M), mitochondria from striatum and liver exhibited state 3 oxygen consumption rates of 101.5 +/- 21.3 and 53.6 +/- 14.8, respectively. On the other hand, MPP+ (0.5 mM) inhibited the NAD-linked substrate (P/M) oxidation in both tissue preparations. MPP+ failed to influence oxidative phosphorylation when succinate was used as the substrate. Mitochondria from liver and striatum exhibited low levels of 45Ca uptake in the absence of Mg.ADP. This was increased by about 3-fold in the presence of Mg.ADP. MPP+ under either condition had very little effect on 45Ca uptake by these organelles.
Thakar
J H
JH
Parkinson's Disease Laboratory, Ottawa Civic Hospital, Ontario, Canada.
Hassan
M N
MN
Grimes
J D
JD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D009498:Neurotoxins; D011725:Pyridines; D011726:Pyridinium Compounds; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium