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

Purpose. To assess the functional characteristics of human organic anion tr ansporter 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-17 beta -glucuronide and estrone-3-sulfate were measu red using radiolabeled compounds. Results. OATP-C transported both estrone-3-sulfate and estradiol-17 beta -g lucuronide, whereas OATP-B transported only the former. OATP-C-mediated upt ake of estrone-3-sulfate exhibited biphasic saturation kinetics, whereas tr ansports of estradiol-17 beta -glucuronide by OATP-C and estrone-3-sulafte by OATP-B followed single-saturation kinetics. Inhibition kinetics showed t hat only the high-affinity site for estrone-3-sulfate on OATP-C was shared with glucuronide conjugates. Uptake of [H-3]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 glucuro nide conjugates, whereas OATP-C transported both types of steroid conjugate s. Transport of estrone-3-sulfate by OATP-B and -C followed single- and bip hasic-saturation kinetics, respectively, and the high-affinity site on OATP -C was the same as that for estradiol-17 beta -glucuronide. Other OATPs, OA TP-A and OATP-8, reportedly exhibit different preferences for steroid conju gates, and the specific recognition of sulfate conjugates seems to be uniqu e to OATP-B.