Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3.

Yasuna Kobayashi, Naomi Ohshiro, Ayumi Tsuchiya, Noriko Kohyama, Masayuki Ohbayashi, Toshinori Yamamoto

Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555.

Drug metabolism and disposition: the biological fate of chemicals 2004 May

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Organic anion transporter 3 [Oat3(Slc22a8)] plays an important role in the renal handling of organic compounds. The substrate specificity of rat Oat3 and human Oat3 has been elucidated; information on mouse Oat3 (mOat3) is less defined. The aim of this study was to extend the substrate selectivity of mOat3. When expressed in Xenopus laevis oocytes, mOat3 mediated the uptake of p-aminohippuric acid and estron sulfate (ES). In addition to these substrates, we found that several organic compounds such as prostaglandin E(2), prostaglandin F(2alpha), allopurinol, 6-mercaptopurine (6-MP), 5-fluorouracil (5-FU), and l-carnitine are substrates of mOat3, compounds identified for the first time. The apparent K(m) values for the uptake of mOat3 that mediated the transport of 6-MP, 5-FU, and l-carnitine were 4.01 +/- 0.7 microM, 53.9 +/- 8.9 nM, and 61.9 +/- 1.1 nM, respectively. Northern blot analysis revealed that gene coding for mOat3 is predominant in the kidney and, to a lesser extent, in the brain and the eye. Our findings thus provide further insights into the role of Oat3 in renal drug transport.

Citation

Yasuna Kobayashi, Naomi Ohshiro, Ayumi Tsuchiya, Noriko Kohyama, Masayuki Ohbayashi, Toshinori Yamamoto. Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug metabolism and disposition: the biological fate of chemicals. 2004 May;32(5):479-83