TY - JOUR
T1 - Accumulation of the 1-methyl-4-phenylpyridinium ion in suncus (Suncus murinus) brain
T2 - Implication for flavin-containing monooxygenase activity in brain microvessels
AU - Mushiroda, T.
AU - Ariyoshi, N.
AU - Yokoi, T.
AU - Takahara, E.
AU - Nagata, O.
AU - Kato, H.
AU - Kamataki, T.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035108215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035108215&partnerID=8YFLogxK
U2 - 10.1021/tx0001225
DO - 10.1021/tx0001225
M3 - Article
C2 - 11258972
AN - SCOPUS:0035108215
SN - 0893-228X
VL - 14
SP - 228
EP - 232
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 2
ER -