Functional characterization of human monocarboxylate transporter 6 (SLC16A5)

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

Research output: Contribution to journalArticle

51 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Bumetanide
nateglinide
Probenecid
torsemide
Lactic Acid
Sodium Potassium Chloride Symporter Inhibitors
Thiazides
Glyburide
Furosemide
Xenopus laevis
Succinic Acid
Tissue Distribution
Substrates
Substrate Specificity
Carboxylic Acids
Tryptophan
Pharmaceutical Preparations
Membrane Potentials
Transport properties
Oocytes

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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

Functional characterization of human monocarboxylate transporter 6 (SLC16A5). / Murakami, Yuichi; Kohyama, Noriko; Kobayashi, Yasuna; Ohbayashi, Masayuki; Ohtani, Hisakazu; Sawada, Yasufumi; Yamamoto, Toshinori.

In: Drug Metabolism and Disposition, Vol. 33, No. 12, 12.2005, p. 1845-1851.

Research output: Contribution to journalArticle

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, vol. 33, no. 12, pp. 1845-1851. https://doi.org/10.1124/dmd.105.005264
Murakami, Yuichi ; Kohyama, Noriko ; Kobayashi, Yasuna ; Ohbayashi, Masayuki ; Ohtani, Hisakazu ; Sawada, Yasufumi ; Yamamoto, Toshinori. / Functional characterization of human monocarboxylate transporter 6 (SLC16A5). In: Drug Metabolism and Disposition. 2005 ; Vol. 33, No. 12. pp. 1845-1851.
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