Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C.

I Tamai, T Nozawa, M Koshida, J Nezu, Y Sai, A Tsuji

Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.

Pharmaceutical research 2001 Sep

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To assess the functional characteristics of human organic anion transporter B (OATP-B) in comparison with those of the known, liver-specific OATP-C. OATP-B or -C was expressed in HEK293 cells or Xenopus oocytes, and uptakes of estradiol-17beta-glucuronide and estrone-3-sulfate were measured using radiolabeled compounds. OATP-C transported both estrone-3-sulfate and estradiol-17beta-glucuronide, whereas OATP-B transported only the former. OATP-C-mediated uptake of estrone-3-sulfate exhibited biphasic saturation kinetics, whereas transports of estradiol-17beta-glucuronide by OATP-C and estrone-3-sulfate 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. 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-17beta-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.

Citation

I Tamai, T Nozawa, M Koshida, J Nezu, Y Sai, A Tsuji. Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharmaceutical research. 2001 Sep;18(9):1262-9