Mechanism of L-lactic Acid Transport in L6 Skeletal Muscle Cells

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  • KOBAYASHI Masaki
    Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University
  • ITAGAKI Shirou
    Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University
  • HIRANO Takeshi
    Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University
  • ISEKI Ken
    Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University

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  L-lactic acid transport plays an important role in the regulation of L-lactic acid circulation into and out of muscle. To clarify the transport mechanism of L-lactic acid in skeletal muscle, L-lactic acid uptake was investigated using a L6 cell line. mRNAs of monocarboxylate transporter (MCT) 1, 2 and 4 were found to be expressed in L6 cells. The [14C] L-lactic acid uptake by L6 cells increased up to pH of 6.0. The [14C] L-lactic acid uptake at pH 6.0 was concentration-dependent with a Km of 3.7 mM. This process was reduced by α-cyano-4-hydroxycinnamate, a typical MCT1, 2 and 4 inhibitor. These results suggest that an MCT participates in the uptake of L-lactic acid by L6 cells. [14C] L-lactic acid uptake was markedly inhibited by monocarboxylic acids and monocarboxylate drugs but not by dicarboxylic acids and amino acids. Moreover, benzoic acid, a substrate for MCT1, competitively inhibited this process with Ki of 1.7 mM. [14C] L-lactic acid efflux in L6 cells was inhibited by α-cyano-4-hydroxycinnamate but not by benzoic acid. These results suggest that [14C] L-lactic acid efflux in L6 cells is mediated by MCT other than MCT1.<br>

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