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A complementary DNA (cDNA) encoding a novel member of organic anion transoporter, OAT-K1, expressed specifically in the kidney of rats was isolated, and the transport characteristics were assessed by LLC-PK, cells stably expressing OAT-K1 (LLC-OAT-K1). The OAT-K1 cDNA (2, 788 bp) consists of a 669-amino acid protein (calculated molecular mass of 74 kDa) which shows 72% identy with the rat liver Na+-independent organic anion transporting polypeptide (oatp). Northern blot analysis and reverse transcription-coupled PCR revealed that the rat OAT-K1 mRNA is expressed predominantly in the kidney medulla, but not in the liver. LLC-OAT-K1 monolayers showed that the OAT-KI mediates basolateral uptake of methotrexate, but not taurocholate, p-aminohippurate, prostaglandin E2, and leukotriene C4. Folate, sulfobromophthalein and DIDS inhibited the methotrexate accumulation markedly. Furthermore, some steroides and nonsteroidal anti-inflammatory drugs showed the potent inhibitory effects on methotrexate uptake by LLC-OAT-K1 monolayers. These findings suggest that the rat OAT-K1 is a new organic anion transporter involved in detoxification process in the kidney, mediating basolateral uptake of anionic xenobiotics.

MOLECULAR ANALYSIS FOR STRUCTURE AND FUNCTION OF RENAL TUBULAR ORGANIC ANION TRANSPORTER, OAT-K1