Abstract
Human monocarboxylate transporter 6 (MCT6) has recently been isolated, and its tissue distribution has been established at the mRNA level, but its functional properties remain unknown. The aim of this study is to investigate the transport properties of MCT6. When expressed in Xenopus laevis oocytes, MCT6 transported [3H]bumetanide in a pH- and membrane potential-sensitive but not proton gradient-dependent manner, with the Kt value of 84 μM. Furthermore, MCT6 transported various drugs such as probenecid and nateglinide. Neither [14C]l-lactic acid nor [3H]l-tryptophan, typical substrates of other MCT isoforms, was transported by MCT6. Four loop diuretics, i.e., furosemide, piretanide, azosemide, and torasemide, thiazides, probenecid, glibenclamide, and nateglinide inhibited the MCT6-mediated uptake of [3H]bumetanide. In contrast, short-chain carboxylic acids, such as l-lactic acid and succinic acid did not inhibit the MCT6-mediated uptake of bumetanide. These results suggest that the substrate specificity of MCT6 is distinct from those of other MCTs. Bumetanide would be a good tool for investigating the functional properties of MCT6. It is probable that MCT6 is involved in the disposition of various drugs, including bumetanide.
Footnotes
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This work was supported in part a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.005264.
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ABBREVIATIONS: MCT, monocarboxylate transporter; TAT1, T-type amino acid transporter 1; PCR, polymerase chain reaction; pHi, intracellular pH; pHo, external pH; ES, estrone-3-sulfate; OAT, organic anion transporter; OATP, organic anion transporting polypeptide; PAH, p-aminohippuric acid.
- Received April 21, 2005.
- Accepted September 16, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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