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Expression and Functional Involvement of Organic Anion Transporting Polypeptide Subtype 3 (Slc21a7) in Rat Choroid Plexus

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Abstract

Purpose. It has been shown that transport(s) are involved in the uptake of estradiol 17β glucuronide (E217βG) by the choroid plexus (CP). The purpose of this study is to compare the substrate specificity of the transporter in the CP with those of rat organic anion transporting polypeptide 1 (rOatp1) and rOatp3.

Methods. The expression of rOatp1 and rOatp3 in rat CP was confirmed by RT-PCR and Western blot analyses. The substrate specificity of rOatp1 and rOatp3 was compared using cDNA-transfected LLC-PK1 cells. The uptake of E217βG by rat isolated CP was determined by centrifugal filtration technique.

Results. PCR analyses demonstrated that the mRNA expression of rOatp3 was abundant in the CP, whereas that of rOatp1 was low. Immunohistochemical staining revealed that rOatp3 is expressed on the apical membrane of the CP. Kinetic parameters (Km and Ki values) of rOatp3 were similar to those for rOatp1. The results of mutual inhibition study suggest that E217βG and taurocholate share the same mechanism in the CP. Corticosterone, estrone-3-sulfate and indomethacin are moderate inhibitors, but no effects by digoxin, p-aminohippurate, benzylpenicillin and cimetidine were observed.

Conclusions. rOatp3 is most possible candidate transporter involved in the uptake of organic anions on the brush border membrane of the choroid epithelial cells.

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Authors and Affiliations

  1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Hiroyuki Kusuhara, Zhonggui He, Yoshinori Nagata, Yoshitane Nozaki & Yuichi Sugiyama

  2. Drug Metabolism & Physicochemical Property Research Laboratory, Daiichi Pharmaceutical, Tokyo, Japan

    Takashi Ito & Hiroyuki Masuda

  3. Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital Zurich, Ramistrasse 100, CH-8091, Zurich, Switzerland

    Peter J. Meier

  4. Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan

    Takaaki Abe

Authors
  1. Hiroyuki Kusuhara
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  2. Zhonggui He
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  3. Yoshinori Nagata
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  4. Yoshitane Nozaki
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  5. Takashi Ito
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  6. Hiroyuki Masuda
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  7. Peter J. Meier
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  8. Takaaki Abe
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  9. Yuichi Sugiyama
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Correspondence to Yuichi Sugiyama.

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Kusuhara, H., He, Z., Nagata, Y. et al. Expression and Functional Involvement of Organic Anion Transporting Polypeptide Subtype 3 (Slc21a7) in Rat Choroid Plexus. Pharm Res 20, 720–727 (2003). https://doi.org/10.1023/A:1023473216759

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