title: Functional characterization of human monocarboxylate transporter 6 (SLC16A5).
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 K(t) value of 84 microM. 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.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Murakami
authors.forename: Noriko
authors.initials: N
authors.lastname: Kohyama
authors.forename: Yasuna
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohbayashi
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ohtani
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sawada
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D027501:Monocarboxylic Acid Transporters / Q000502:physiology*; D013379:Substrate Specificity; D014981:Xenopus
chemical_list: D027501:Monocarboxylic Acid Transporters; D002034:Bumetanide