title: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555.
authors.forename: Yasuna
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohshiro
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Noriko
authors.initials: N
authors.lastname: Kohyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohbayashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000493:Allopurinol / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D000493:Allopurinol