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-17beta-glucuronide and estrone-3-sulfate were measured using radiolabeled compounds. RESULTS: 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. 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-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.
PURPOSE: To assess the functional characteristics of humanorganic 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-17beta-glucuronide and estrone-3-sulfate were measured using radiolabeled compounds. RESULTS: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. 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-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.
Authors: T Nishio; H Adachi; R Nakagomi; T Tokui; E Sato; M Tanemoto; K Fujiwara; M Okabe; T Onogawa; T Suzuki; D Nakai; K Shiiba; M Suzuki; H Ohtani; Y Kondo; M Unno; S Ito; K Iinuma; K Nunoki; S Matsuno; T Abe Journal: Biochem Biophys Res Commun Date: 2000-09-07 Impact factor: 3.575
Authors: T Abe; M Kakyo; T Tokui; R Nakagomi; T Nishio; D Nakai; H Nomura; M Unno; M Suzuki; T Naitoh; S Matsuno; H Yawo Journal: J Biol Chem Date: 1999-06-11 Impact factor: 5.157
Authors: T Iwatsubo; H Suzuki; N Shimada; K Chiba; T Ishizaki; C E Green; C A Tyson; T Yokoi; T Kamataki; Y Sugiyama Journal: J Pharmacol Exp Ther Date: 1997-08 Impact factor: 4.030
Authors: Y Sai; T Nishimura; S Shimpo; T Chishu; K Sato; N Kose; T Terasaki; C Mukai; S Kitagaki; N Miyakoshi; Y-S Kang; E Nakashima Journal: Pharm Res Date: 2008-03-12 Impact factor: 4.200