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Functional characterization and tissue localization of a novel liver‐specific organic anion transporter OAT7
Author(s) -
Shin Ho Jung,
Anzai Naohiko,
He Xin,
Kanai Yoshikatsu,
Endou Hitoshi
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a840-c
Subject(s) - organic anion , chemistry , organic anion transporter 1 , transporter , xenobiotic , biochemistry , xenopus , organic anion transporting polypeptide , glutathione , estrone sulfate , membrane transport , hepatocyte , estrone , membrane , hormone , enzyme , ion , in vitro , organic chemistry , gene
The multispecific transporters in the liver play an important role in the elimination of toxic substances and in the turnover of endogenous biomolecules. Uptake of organic anions across the sinusoidal membrane is mediated in large part by three classes of proteins: OATP, NTCP, and OAT family of proteins. In this study, we identify a novel organic anion transporter OAT7 exclusively expressing in human liver. OAT7 showed 35% to 46% identities to those of other members of OAT family. When expressed in Xenopus oocytes, OAT7 mediated high affinity transport of sulfate‐conjugated steroid hormones, estrone sulfate (ES) (Km = 8.7 μM) and DHEA sulfate (Km = 2.2 μM), in a sodium independent manner, whereas it did not transport other organic anions. ES transport mediated by OAT7 was inhibited by negatively charged BSP, ICG and several sulfate‐conjugated xenobiotics. In contrast, glucuronide and glutathione conjugates exhibited no inhibitory effects on the OAT7‐mediated transport. Immunohistochemical analysis revealed that OAT7 protein was located in the sinusoidal membrane of hepatocytes. We further examined the trans ‐stimulatory effects of various endogenous organic anions to investigate the driving force for OAT7‐mediated transport. Short chain fatty acids trans ‐stimulated the OAT7‐mediated ES uptake by the injection of those cold compounds into the oocytes. These results suggest that OAT7 is the liver‐specific organic anion transporter using some organic anions as a counterion for its exchange mechanism.