Accumulation of the 1-methyl-4-phenylpyridinium ion in suncus (Suncus murinus) brain: implication for flavin-containing monooxygenase activity in brain microvessels

Chem Res Toxicol. 2001 Feb;14(2):228-32. doi: 10.1021/tx0001225.

Abstract

The metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was examined in an effort to evaluate the role of flavin-containing monooxygenase (FMO) expressed in the brain of suncus (Suncus murinus) and rats. MPTP was metabolized to generate both 1-methyl-4-phenylpyridinium ion (MPP(+)) and MPTP N-oxide by brain homogenates from rats. Although the level of MPP(+)-producing activity was similar in suncus and rats, a remarkable difference was found between the animal species in MPTP N-oxygenase activity, which was not detectable in brain homogenates from suncus. The concentrations of MPP(+) in suncus brain after a single ip administration of MPTP were markedly higher than that in rats, probably because of the lack of FMO activity in the suncus brain. The MPTP N-oxygenase activity of microvessel homogenates of rat brain was 21-fold greater than that of whole brain homogenates. These results suggest that FMO(s) plays a significant role in the detoxification of MPTP in cerebral endothelial cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / blood
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / metabolism
  • 1-Methyl-4-phenylpyridinium / pharmacokinetics*
  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Animals
  • Brain / enzymology
  • Brain / metabolism*
  • Capillaries / enzymology
  • Capillaries / metabolism
  • Hot Temperature
  • Male
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Shrews / physiology*
  • Species Specificity

Substances

  • Monoamine Oxidase Inhibitors
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Monoamine Oxidase
  • 1-Methyl-4-phenylpyridinium