Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), cyperquat (MPP+) and paraquat on isolated mitochondria from rat striatum, cortex and liver.
The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite 1-methyl-4-phenyl pyridinium ion (MPP+, cyperquat) and a structurally-related compound paraquat on mitochondrial functions were investigated in isolated organelles from rat striatum, cortex and liver. MPTP (0.1-1.0 mM) had no significant effect on various parameters of mitochondrial oxidative phosphorylation. In contrast, MPP+ (0.5 mM) inhibited the oxidation of the nicotinamide adenine dinucleotide (NAD+)-linked substrates pyruvate and malate but not that of the flavin adenine dinucleotide (FAD+)-linked substrate succinate. Paraquat (5.0 mM) significantly stimulated basal oxygen consumption (state 4) without influencing the oxygen utilization (state 3) associated with adenosine diphosphate (ADP) phosphorylation. Thus, these structurally-related compounds have different effects on mitochondrial oxidative phosphorylation, but the organelles from striatum, cortex and liver were affected in a similar manner by these compounds.
Thakar
J H
JH
Parkinson's Disease Research Laboratory, Ottawa Civic Hospital, Ontario, Canada.
Hassan
M N
MN
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000648:ultrastructure; D003342:Corpus Striatum / Q000648:ultrastructure; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D008293:Malates; D011725:Pyridines; D011726:Pyridinium Compounds; D011773:Pyruvates; D013386:Succinates; D009243:NAD; D005182:Flavin-Adenine Dinucleotide; D000244:Adenosine Diphosphate; C030298:malic acid; D019289:Pyruvic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019802:Succinic Acid; D010269:Paraquat; D015655:1-Methyl-4-phenylpyridinium