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

T. Mushiroda, Noritaka Ariyoshi, T. Yokoi, E. Takahara, O. Nagata, H. Kato, T. Kamataki

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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.

Original languageEnglish
Pages (from-to)228-232
Number of pages5
JournalChemical Research in Toxicology
Volume14
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Toxicology

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