Mechanism of L-lactic acid transport in L6 skeletal muscle cells.
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 [(14)C] L-lactic acid uptake by L6 cells increased up to pH of 6.0. The [(14)C] L-lactic acid uptake at pH 6.0 was concentration-dependent with a K(m) of 3.7 mM. This process was reduced by alpha-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. [(14)C] 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 K(i) of 1.7 mM. [(14)C] L-lactic acid efflux in L6 cells was inhibited by alpha-cyano-4-hydroxycinnamate but not by benzoic acid. These results suggest that [(14)C] L-lactic acid efflux in L6 cells is mediated by MCT other than MCT1.
Kobayashi
Masaki
M
Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Sapporo 060-0812, Japan.
Itagaki
Shirou
S
Hirano
Takeshi
T
Iseki
Ken
K
D000818:Animals; D019817:Benzoic Acid / Q000494:pharmacology; D001693:Biological Transport, Active; D002264:Carboxylic Acids / Q000494:pharmacology; D002460:Cell Line; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature
D002264:Carboxylic Acids; D019344:Lactic Acid; D019817:Benzoic Acid