RT Journal Article
SR Electronic
T1 RENAL TRANSPORT OF ORGANIC COMPOUNDS MEDIATED BY MOUSE ORGANIC ANION TRANSPORTER 3 (MOAT3): FURTHER SUBSTRATE SPECIFICITY OF MOAT3
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 479
OP 483
DO 10.1124/dmd.32.5.479
VO 32
IS 5
A1 Yasuna Kobayashi
A1 Naomi Ohshiro
A1 Ayumi Tsuchiya
A1 Noriko Kohyama
A1 Masayuki Ohbayashi
A1 Toshinori Yamamoto
YR 2004
UL http://dmd.aspetjournals.org/content/32/5/479.abstract
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