Expression and function of TETRAN, a new type of membrane transporter |
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Authors: | Ushijima Hironori Hiasa Miki Namba Takushi Hwang Hyun-Jung Hoshino Tatsuya Mima Shinji Tsuchiya Tomofusa Moriyama Yoshinori Mizushima Tohru |
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Affiliation: | a Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan b Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan |
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Abstract: | In contrast to transport across basolateral membranes, the mechanism governing transport of organic anions across the luminal membranes of proximal tubules has remained unclear. We recently found Tetracycline transporter-like protein (TETRAN), a human ortholog of yeast Tpo1p that can transport anionic Non-steroidal anti-inflammatory drugs (NSAIDs). In this study, we examine the expression and function of TETRAN. TETRAN mRNA is expressed in various human tissues, including kidney. When overexpressed in cultured cells, TETRAN was predominantly localized on cytoplasmic membranes. Immunohistochemical analysis of human and mouse kidney tissue showed that TETRAN was expressed at the luminal membranes of proximal tubules. Overexpression of TETRAN in cultured cells facilitated the uptake of organic anions such as indomethacin (a NSAID) and fluorescein. The results suggest that TETRAN is a novel human organic anion transporter, and that it serves as a transporter for some NSAIDs and various other organic anions at the final excretion step. |
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Keywords: | ABC, ATP binding cassette COX, cyclooxygenase MATE, multidrug and toxin extrusion MFS, major facilitator super-family MRP, multidrug resistance-associated protein NPT, sodium-dependent inorganic phosphate transporter NSAID, non-steroidal anti-inflammatory drug OAT, organic anion transporter PAH, p-aminohippuric acid TEA, tetraethylammonium bromide TETRAN, tetracycline transporter-like protein |
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