PT  - JOURNAL ARTICLE
AU  - Yasuna Kobayashi
AU  - Naomi Ohshiro
AU  - Ayumi Tsuchiya
AU  - Noriko Kohyama
AU  - Masayuki Ohbayashi
AU  - Toshinori Yamamoto
TI  - RENAL TRANSPORT OF ORGANIC COMPOUNDS MEDIATED BY MOUSE ORGANIC ANION TRANSPORTER 3 (MOAT3): FURTHER SUBSTRATE SPECIFICITY OF MOAT3
AID  - 10.1124/dmd.32.5.479
DP  - 2004 May 01
TA  - Drug Metabolism and Disposition
PG  - 479--483
VI  - 32
IP  - 5
4099  - http://dmd.aspetjournals.org/content/32/5/479.short
4100  - http://dmd.aspetjournals.org/content/32/5/479.full
SO  - Drug Metab Dispos2004 May 01; 32
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics