Lactic Acid Efflux from White Skeletal Muscle Is Catalyzed by the Monocarboxylate Transporter Isoform MCT3*

The newly cloned proton-linked monocarboxylate transporter MCT3 was shown by Western blotting and immunofluorescence confocal microscopy to be expressed in all muscle fibers. In contrast, MCT1 is expressed most abundantly in oxidative fibers but is almost totally absent in fast-twitch glycolytic fibers. Thus MCT3 appears to be the major MCT isoform responsible for efflux of glycolytically derived lactic acid from white skeletal muscle. MCT3 is also expressed in several other tissues requiring rapid lactic acid efflux. The expression of both MCT3 and MCT1 was decreased by 40–60% 3 weeks after denervation of rat hind limb muscles, whereas chronic stimulation of the muscles for 7 days increased expression of MCT1 2–3-fold but had no effect on MCT3 expression. The kinetics and substrate and inhibitor specificities of monocarboxylate transport into cell lines expressing only MCT3 or MCT1 have been determined. Differences in the properties of MCT1 and MCT3 are relatively modest, suggesting that the significance of the two isoforms may be related to their regulation rather than their intrinsic properties.

[1]  N. Price,et al.  Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. , 1998, The Biochemical journal.

[2]  X Wang,et al.  Lactate transport in heart in relation to myocardial ischemia. , 1997, The American journal of cardiology.

[3]  H. Kleinman,et al.  Thrombin promotes endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo. , 1997, The American journal of physiology.

[4]  A. Halestrap,et al.  Interaction of the Erythrocyte Lactate Transporter (Monocarboxylate Transporter 1) with an Integral 70-kDa Membrane Glycoprotein of the Immunoglobulin Superfamily* , 1997, The Journal of Biological Chemistry.

[5]  L. Carpenter,et al.  Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides evidence that expression in tissues is species-specific and may involve post-transcriptional regulation. , 1997, The Biochemical journal.

[6]  N. Philp,et al.  Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium. , 1997, Biochemical and biophysical research communications.

[7]  C. Juel.  Lactate-proton cotransport in skeletal muscle. , 1997, Physiological reviews.

[8]  C. Sansom,et al.  Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1). , 1996, The Biochemical journal.

[9]  C. Juel.  Symmetry and pH dependency of the lactate/proton carrier in skeletal muscle studied with rat sarcolemmal giant vesicles. , 1996, Biochimica et biophysica acta.

[10]  W. Gilmour,et al.  Quantitative skeletal muscle histochemistry of four east African ruminants. , 1996, Journal of anatomy.

[11]  L. Carpenter,et al.  Cloning and sequencing of the monocarboxylate transporter from mouse Ehrlich Lettré tumour cell confirms its identity as MCT1 and demonstrates that glycosylation is not required for MCT1 function. , 1996, Biochimica et biophysica acta.

[12]  A. Halestrap,et al.  The Kinetics, Substrate, and Inhibitor Specificity of the Monocarboxylate (Lactate) Transporter of Rat Liver Cells Determined Using the Fluorescent Intracellular pH Indicator, 2′,7′-Bis(carboxyethyl)-5(6)-carboxyfluorescein (*) , 1996, The Journal of Biological Chemistry.

[13]  N. Price,et al.  cDNA cloning of MCT1, a monocarboxylate transporter from rat skeletal muscle. , 1995, Biochimica et biophysica acta.

[14]  D. Boettiger,et al.  Developmental expression and molecular cloning of REMP, a novel retinal epithelial membrane protein. , 1995, Experimental cell research.

[15]  M. Brown,et al.  cDNA Cloning of MCT2, a Second Monocarboxylate Transporter Expressed in Different Cells than MCT1 (*) , 1995, The Journal of Biological Chemistry.

[16]  L. Carpenter,et al.  The kinetics, substrate and inhibitor specificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF. , 1994, The Biochemical journal.

[17]  U. Francke,et al.  cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12. , 1994, Genomics.

[18]  Richard G. W. Anderson,et al.  Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: Implications for the Cori cycle , 1994, Cell.

[19]  A. Halestrap,et al.  Transport of lactate and other monocarboxylates across mammalian plasma membranes. , 1993, The American journal of physiology.

[20]  A J Levi,et al.  Characterization of the inhibition by stilbene disulphonates and phloretin of lactate and pyruvate transport into rat and guinea-pig cardiac myocytes suggests the presence of two kinetically distinct carriers in heart cells. , 1993, The Biochemical journal.

[21]  A. Halestrap,et al.  Identification and partial purification of the erythrocyte L-lactate transporter. , 1992, The Biochemical journal.

[22]  F. A. Doyle,et al.  Reconstitution and identification of the major Na(+)-dependent neutral amino acid-transport protein from bovine renal brush-border membrane vesicles. , 1992, The Biochemical journal.

[23]  H. Pilegaard,et al.  Muscle lactate transport studied in sarcolemmal giant vesicles: dependence on fibre type and age. , 1991, Acta physiologica Scandinavica.

[24]  J. Tavaré,et al.  The regulatory role of known tyrosine autophosphorylation sites of the insulin receptor kinase domain. An assessment by replacement with neutral and negatively charged amino acids. , 1991, The Journal of biological chemistry.

[25]  R. Thomas,et al.  A microelectrode study of the mechanisms of L‐lactate entry into and release from frog sartorius muscle. , 1988, The Journal of physiology.

[26]  R. Armstrong,et al.  Muscle fiber type composition of the rat hindlimb. , 1984, The American journal of anatomy.