Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]).
Human organic anion transporter 2 (hOat2[SLC22A7]) is highly expressed in the human liver. Although localization, gene expression, substrate specificity and transport mechanisms of other human Oat isoforms such as human Oat1 (hOat1), human Oat3 (hOat3) and human Oat4 (hOat4) have been elucidated, information concerning human Oat2 (hOat2) is less defined. The objective of this study was to provide further information on the transport mechanism and substrate specificity of hOat2. When expressed in Xenopus laevis oocytes, the transport of organic compounds mediated by hOat2 was not affected by the replacement of extracellular sodium with lithium, choline and mannitol. The uptake of estrone sulfate (ES) in hOat2-expressing oocytes was significantly trans-stimulated by preloading the oocytes with fumarate and succinate, but not glutarate. Moreover, we observed that hOat2 mediates the transport of bumetanide, ES, glutarate, dehydroepiandrosterone sulfate, allopurinol, prostaglandin E2, 5-fluorouracil, paclitaxel and L-ascorbic acid. These compounds are identified for the first time as hOat2 substrates. A wide range of structurally unrelated organic compounds inhibited the hOat2-mediated uptake of tetracycline, except for sulfobromophthalein. All of these findings indicate that hOat2 is a sodium-independent multi-specific organic anion/dimethyldicarboxylate exchanger. Our present findings thus provide further insights into the role of hOat2 in hepatic drug transport.
Kobayashi
Yasuna
Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Ohshiro
Naomi
N
Sakai
Ryoko
R
Ohbayashi
Masayuki
M
Kohyama
Noriko
N
Yamamoto
Toshinori
T
D000818:Animals; D001693:Biological Transport, Active; D002412:Cations / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D013379:Substrate Specificity; D014982:Xenopus laevis
D002412:Cations; D003998:Dicarboxylic Acids; D027381:Liver-Specific Organic Anion Transporter 1