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Substrate Specificity of Organic Anion Transporter 2: A Tale of Different Expression Systems?
Author(s) -
Pelis Ryan M
Publication year - 2010
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.24.1_supplement.609.2
Subject(s) - xenopus , organic anion transporter 1 , chinese hamster ovary cell , biology , transporter , estrone sulfate , organic anion transporting polypeptide , hek 293 cells , organic anion , cell culture , biochemistry , estrone , chemistry , endocrinology , receptor , hormone , gene , ion , genetics , organic chemistry
The organic anion transporter 2 (OAT2) has been suggested to play an important role in the hepatic elimination of thereapeutic drugs. Available data on OAT2 substrate specificity largely comes from its expression in Xenopus laevis oocytes. The human ortholog of OAT2 (hOAT2) was cloned from human liver and stably expressed in Chinese hamster ovary (CHO) cells and human embryonic kidney (HEK) cells to further define its substrate specificity. hOAT2 mRNA was abundant in the stably selected cells (real‐time PCR), and immunocytochemical localization was consistent with plasma membrane expression. hOAT2‐mediated transport of organic anions that had previously been shown to be transported by hOAT2 in Xenopus oocytes was low to absent, i.e., estrone‐3‐sulfate, taxol and dehydroepiandrosterone. Additionally, several other drugs were tested for their interaction with hOAT2 in these expression systems (e.g., estradiol 17β D‐glucuronide, vinblastine, taurocholate, adefovir, atorvastatin and diclofenac), and the transport protein had little impact on their accumulation in the stable cells. Differences in the substrate specificity of OAT2 expressed in Xenopus oocytes versus mammalian cell lines are apparent. Further investigation is required to determine the substrate specificity and role of OAT2, a mystery transporter, in the hepatic excretion of xenobiotics.