Inhibition of mitochondrial respiration by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse brain in vivo.
This is the first report on in vivo effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mitochondrial respiration in mouse brain. C57/BL mice, injected with 40 mg/kg of MPTP subcutaneously, were sacrificed by cervical dislocation 5-6 h after the injection. Mitochondrial suspensions were prepared from whole brains. Mitochondrial respiration was studied polarographically. The state 3 respiration, i.e., the active respiration in the presence of tricarboxylic acid (TCA) cycle substrates and ADP with coupled phosphorylation of ADP to ATP, was significantly inhibited in mice treated with MPTP. This inhibition was prevented by pretreatment of mice with pargyline. Activity of mitochondrial NADH-ubiquinone oxidoreductase was also inhibited in mice treated with MPTP.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000187:drug effects; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone); D010293:Pargyline / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011808:Quinone Reductases / Q000378:metabolism; D013997:Time Factors
D011725:Pyridines; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008291:Malate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases