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 E2, prostaglandin F2α, allopurinol, 6-mercaptopurine (6-MP), 5-fluorouracil (5-FU), and l-carnitine are substrates of mOat3, compounds identified for the first time. The apparent Km values for the uptake of mOat3 that mediated the transport of 6-MP, 5-FU, and l-carnitine were 4.01 ± 0.7 μM, 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.
Footnotes
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↵1 Abbreviations used are: OATP, organic anion-transporting polypeptide; dCTP, deoxycytidine [5′-α-32P]triphosphate; ES, estron sulfate; 5-FU, 5-fluorouracil; hOat, human organic anion transporter; 6-MP, 6-mercaptopurine; mOat, mouse organic anion transporter; Oat, organic anion transporter; OCT, organic cation transporter; PAH, p-aminohippuric acid; PG, prostaglandin; rOat, rat organic anion transporter.
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This work was supported in part by Grants-in-Aid from the Nakatomi Foundation (H13).
- Received November 21, 2003.
- Accepted January 16, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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