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Research ArticleArticle

Expression and Functional Characterization of Rat Organic Anion Transporter 3 (rOat3) in the Choroid Plexus

Yoshinori Nagata, Hiroyuki Kusuhara, Hitoshi Endou and Yuichi Sugiyama
Molecular Pharmacology May 2002, 61 (5) 982-988; DOI: https://doi.org/10.1124/mol.61.5.982
Yoshinori Nagata
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Hiroyuki Kusuhara
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Hitoshi Endou
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Yuichi Sugiyama
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Abstract

We reported previously that an efficient efflux system for benzylpenicillin (PCG) is located on the choroid plexus (CP). In this study, we investigated the involvement of rat organic anion transporter 1 (rOat1; Slc22a6) and rOat3 (Slc22a8) in the uptake of PCG and p-aminohippurate (PAH) by the CP. Western blot analysis indicates the expression of rOat3, but not rOat1, on the CP, and immunohistochemical staining shows that rOat3 is localized on the brush border membrane of the choroid epithelial cells. PCG and PAH were found to be taken up by isolated rat CP, withK m values of 111 and 354 μM, respectively. A mutual inhibition study suggests that the same transporter is responsible for the uptake of PCG and PAH by isolated rat CP. This was confirmed by examining the effect of organic anions and cimetidine on their uptake. Estradiol-17β-glucuronide and cimetidine were found to be selective inhibitors of rOat3. The inhibition constants of the inhibitors including estradiol-17β-glucuronide and cimetidine were comparable for the uptake of PAH and PCG by isolated rat CP. In addition, these values were also comparable with those for rOat3, but not with those for rOat1. These results suggest that rOat3 is mainly responsible for the uptake of PCG and PAH by isolated rat CP, and it functions as one of the detoxification systems on the CP by removing its substrates from the cerebrospinal fluid.

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Molecular Pharmacology: 61 (5)
Molecular Pharmacology
Vol. 61, Issue 5
1 May 2002
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Research ArticleArticle

Expression and Functional Characterization of Rat Organic Anion Transporter 3 (rOat3) in the Choroid Plexus

Yoshinori Nagata, Hiroyuki Kusuhara, Hitoshi Endou and Yuichi Sugiyama
Molecular Pharmacology May 1, 2002, 61 (5) 982-988; DOI: https://doi.org/10.1124/mol.61.5.982

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Research ArticleArticle

Expression and Functional Characterization of Rat Organic Anion Transporter 3 (rOat3) in the Choroid Plexus

Yoshinori Nagata, Hiroyuki Kusuhara, Hitoshi Endou and Yuichi Sugiyama
Molecular Pharmacology May 1, 2002, 61 (5) 982-988; DOI: https://doi.org/10.1124/mol.61.5.982
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