RT Journal Article
SR Electronic
T1 FUNCTIONAL CHARACTERIZATION OF HUMAN MONOCARBOXYLATE TRANSPORTER 6 (<em>SLC16A</em>5)
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1845
OP 1851
DO 10.1124/dmd.105.005264
VO 33
IS 12
A1 Yuichi Murakami
A1 Noriko Kohyama
A1 Yasuna Kobayashi
A1 Masayuki Ohbayashi
A1 Hisakazu Ohtani
A1 Yasufumi Sawada
A1 Toshinori Yamamoto
YR 2005
UL http://dmd.aspetjournals.org/content/33/12/1845.abstract
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