PT  - JOURNAL ARTICLE
AU  - Yuichi Murakami
AU  - Noriko Kohyama
AU  - Yasuna Kobayashi
AU  - Masayuki Ohbayashi
AU  - Hisakazu Ohtani
AU  - Yasufumi Sawada
AU  - Toshinori Yamamoto
TI  - FUNCTIONAL CHARACTERIZATION OF HUMAN MONOCARBOXYLATE TRANSPORTER 6 (<em>SLC16A</em>5)
AID  - 10.1124/dmd.105.005264
DP  - 2005 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 1845--1851
VI  - 33
IP  - 12
4099  - http://dmd.aspetjournals.org/content/33/12/1845.short
4100  - http://dmd.aspetjournals.org/content/33/12/1845.full
SO  - Drug Metab Dispos2005 Dec 01; 33
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics