Functional characterization of human monocarboxylate transporter 6 (SLC16A5)

Yuichi Murakami, Noriko Kohyama, Yasuna Kobayashi, Masayuki Ohbayashi, Hisakazu Ohtani, Yasufumi Sawada, Toshinori Yamamoto

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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.

Original languageEnglish
Pages (from-to)1845-1851
Number of pages7
JournalDrug Metabolism and Disposition
Volume33
Issue number12
DOIs
Publication statusPublished - 2005 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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    Murakami, Y., Kohyama, N., Kobayashi, Y., Ohbayashi, M., Ohtani, H., Sawada, Y., & Yamamoto, T. (2005). Functional characterization of human monocarboxylate transporter 6 (SLC16A5). Drug Metabolism and Disposition, 33(12), 1845-1851. https://doi.org/10.1124/dmd.105.005264