Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium ion on activities of the enzymes in the electron transport system in mouse brain

• Published in: Journal of neurochemistry Vol. 48; no. 6; p. 1787
• Main Authors: Mizuno, Y, Sone, N, Saitoh, T
• Format: Journal Article
• Language: English
• Published: England 01.06.1987
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-Methyl-4-phenylpyridinium; Animals; Brain - drug effects; Electron Transport - drug effects; Freezing; Kinetics; Male; Mice; Mice, Inbred C57BL; Mitochondria - drug effects; NAD(P)H Dehydrogenase (Quinone); Oxidoreductases - metabolism; Pyridines - pharmacology; Pyridinium Compounds - pharmacology; Quinone Reductases - antagonists & inhibitors; Quinone Reductases - metabolism; Superoxide Dismutase - pharmacology
• ISSN: 0022-3042
• DOI: 10.1111/j.1471-4159.1987.tb05737.x

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) on activities of enzyme complexes in the electron transport system were studied using isolated mitochondrial preparations from C57BL/6J mouse brains. Both MPTP and MPP+ dose-dependently inhibited activity of NADH-ubiquinone oxidoreductase (EC 1.6.5.3). The inhibition was reversible. Preincubation of freeze-thawed mitochondria with MPTP or MPP+ had no effect on the inhibition; however, when nonfrozen mitochondria were used, NADH-ubiquinone oxidoreductase activity was reduced to 46% of that in the nonincubated sample after a 5-min preincubation with MPTP and to 77% of that in the nonincubated sample after a 5-min preincubation with MPP+. Kinetic analyses revealed that inhibition of MPTP was noncompetitive and that of MPP+ uncompetitive with respect to NADH. On the other hand, inhibition of MPTP was uncompetitive and that of MPP+ noncompetitive with respect to ubiquinone. Succinate-ubiquinone oxidoreductase (complex II), dihydroubiquinone-cytochrome c oxidoreductase (complex III), and ferrocytochrome c-oxygen oxidoreductase (EC 1.9.3.1) activities were either slightly inhibited or not inhibited by MPTP or MPP+. The significance of these findings is discussed in relation to the mechanism of MPTP-induced neuronal degeneration.