Lack of Contribution of P-Glycoprotein (P-gp) to Transport via the Mouse Blood-Cerebrospinal Fluid Barrier
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概要
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The blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) work effectively to restrict the free exchange of compounds between blood and brain. It is well known that P-glycoprotein (P-gp) that is expressed in brain microvessel endothelial cells contributes to the BBB as an efflux transporter. Western blot analysis has shown that P-gp is also expressed in the choroid plexus forming the blood-CSF barrier. The purpose of this study was to examine the role of P-gp in the efflux transport of its substrates across the blood-CSF barrier. The CSF concentration of etoposide and digoxin after intracerebroventricular administration, and the CSF concentration of ^<99m>Tc-sestamibi after intravenous administration were compared between wild-type and P-gp knockout mice. After intra- cerebroventricular administration, there was no significant difference in the remaining concentration of etoposide and digoxin in CSF between wild-type and P-gp knockout mice, respectively. After intravenous administration of ^<99m>Tc-sestamibi, its CSF-to-serum concentration ratio in P-gp knockout mice was not significantly different from that in wild-type, whereas its brain-to-serum concentration ratio was significantly increased in P-gp knockout mice compared with wild-type mice (1.62-fold, p<0.05). In addition, immunohistochemical analysis showed a low membrane expression of P-gp in mouse choroid plexus, compared with brain microvessels. These results suggest that P-gp does not play an important role in the transport of its substrates across the blood-CSF barrier.
- 公益社団法人日本薬学会の論文
- 2005-02-01
著者
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SUGIYAMA Yuichi
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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KUSUHARA Hiroyuki
Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University
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Lee Young-joo
Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Lee Young-Joo
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, the University of Tokyo
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Kusuhara Hiroyuki
Graduate School Of Pharmaceutical Sciences The Univ. Of Tokyo
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Kusuhara H
Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Kusuhara Hiroyuki
Department Of Molecular Pharmacokinetics Graduate School Of Pharmaceutical Sciences The University O
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Sugiyama Yuichi
Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Sugiyama Yuichi
Department Of Applied Biological Science Faculty Of Science And Technology Science University Of Tok
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Kusuhara Hiroyuki
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, the University of Tokyo
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