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

J Neurochem. 1987 Jun;48(6):1787-93. doi: 10.1111/j.1471-4159.1987.tb05737.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Pyridines
  • Pyridinium Compounds
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Oxidoreductases
  • Superoxide Dismutase
  • NAD(P)H Dehydrogenase (Quinone)
  • Quinone Reductases
  • 1-Methyl-4-phenylpyridinium