Accumulation of the 1-methyl-4-phenylpyridinium ion in suncus (Suncus murinus) brain: implication for flavin-containing monooxygenase activity in brain microvessels.
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.
Laboratory of Drug Metabolism, Division of Pharmacobio-dynamics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
T
T
Mushiroda
N
N
Ariyoshi
T
T
Yokoi
E
E
Takahara
O
O
Nagata
H
H
Kato
T
T
Kamataki
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000097:blood / Q000378:metabolism; D015655:1-Methyl-4-phenylpyridinium / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002196:Capillaries / Q000201:enzymology / Q000378:metabolism; D006358:Hot Temperature; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012788:Shrews / Q000502:physiology*; D013045:Species Specificity
D008996:Monoamine Oxidase Inhibitors; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium