Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C.
OBJECTIVE
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.
Tamai
I
I
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Nozawa
T
T
Koshida
M
M
Nezu
J
J
Sai
Y
Y
Tsuji
A
A
D000465:Algorithms; D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D027381:Liver-Specific Organic Anion Transporter 1 / Q000032:analysis / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D014981:Xenopus
D004966:Estrogens, Conjugated (USP); D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C450859:SLCO2B1 protein, human; C025483:estradiol-17 beta-glucuronide; D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate