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Functional Characterization of Human Organic Anion Transporting Polypeptide B (OATP-B) in Comparison with Liver-Specific OATP-C

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Abstract

Purpose. To assess the functional characteristics of human organic anion transporter B (OATP-B) in comparison with those of the known, liver-specific OATP-C.

Methods. OATP-B or -C was expressed in HEK293 cells or Xenopus oocytes, and uptakes of estradiol-17β-glucuronide and estrone-3-sulfate were measured using radiolabeled compounds.

Results. OATP-C transported both estrone-3-sulfate and estradiol-17β-glucuronide, whereas OATP-B transported only the former. OATP-C-mediated uptake of estrone-3-sulfate exhibited biphasic saturation kinetics, whereas transports of estradiol-17β-glucuronide by OATP-C and estrone-3-sulafte by OATP-B followed single-saturation kinetics. Inhibition kinetics showed that only the high-affinity site for estrone-3-sulfate on OATP-C was shared with glucuronide conjugates. Uptake of [3H]estrone-3-sulfate by OATP-B was inhibited by sulfate conjugates but not by glucuronide conjugates, whereas its uptake by OATP-C was inhibited by both types of conjugates.

Conclusions. OATP-B accepted sulfate conjugates of steroids but not glucuronide conjugates, whereas OATP-C transported both types of steroid conjugates. Transport of estrone-3-sulfate by OATP-B and -C followed single- and biphasic-saturation kinetics, respectively, and the high-affinity site on OATP-C was the same as that for estradiol-17β-glucuronide. Other OATPs, OATP-A and OATP-8, reportedly exhibit different preferences for steroid conjugates, and the specific recognition of sulfate conjugates seems to be unique to OATP-B.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, 920-0934, Japan

    Ikumi Tamai, Takashi Nozawa, Minako Koshida, Yoshimichi Sai & Akira Tsuji

  2. CREST, Japan Science and Technology Corporation, Kawaguchi, 332-0012, Japan

    Ikumi Tamai & Akira Tsuji

  3. Chugai Research Institute for Molecular Medicine Inc., Ibaraki, 300-4101, Japan

    Jun-ichi Nezu

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  1. Ikumi Tamai
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Tamai, I., Nozawa, T., Koshida, M. et al. Functional Characterization of Human Organic Anion Transporting Polypeptide B (OATP-B) in Comparison with Liver-Specific OATP-C. Pharm Res 18, 1262–1269 (2001). https://doi.org/10.1023/A:1013077609227

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