Characterization of monocarboxylate transport in human kidney HK-2 cells

Mol Pharm. 2006 Nov-Dec;3(6):675-85. doi: 10.1021/mp060037b.


The objectives of this study were to characterize the expression and function of monocarboxylate transporters (MCTs) in human kidney HK-2 cells and to compare the expression of MCTs in HK-2 cells to that found in human kidney. mRNA and protein expression of MCTs were determined by RT-PCR and Western analyses, respectively, while immunofluorescence staining was used to determine the membrane localization of MCT1. The driving force, transport kinetics, and inhibition of two MCT substrates, D-lactate and butyrate, were characterized in HK-2 cells. mRNA of MCT1, -2, -3, -4 isoforms were present in HK-2 cells and in human kidney cortex. MCT1 was present predominantly on the basal membranes of HK-2 cells. The cellular uptake of D-lactate and butyrate exhibited pH- and concentration-dependence (D-lactate, Km of 26.5 +/- 2.2 mM and Vmax of 72.0 +/- 14.5 nmol mg-1 min-1; butyrate, Km of 0.8 +/- 0.3 mM, Vmax of 29.3 +/- 2.5 nmol mg-1 min-1, and a diffusional clearance of 2.1 microL mg-1 min-1). The uptake of D-lactate and butyrate by HK-2 cells was inhibited by MCT analogues and the classical MCT inhibitors alpha-cyano-4-hydroxycinnamate, pCMB, and phloretin. The uptake of D-lactate and butyrate by HK-2 cells significantly decreased after transfection with small-interference RNA for MCT1. In summary, MCTs were present in both HK-2 cells and human kidney cortex, and HK-2 cells exhibited polarized MCT expression and pH-dependent transport of D-lactate and butyrate. Our results also support the usefulness of HK-2 cells as an in vitro model for studying monocarboxylate transport in renal proximal tubule cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / physiology*
  • Butyrates / pharmacokinetics
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / physiology
  • Kidney Cortex / metabolism
  • Kidney Cortex / physiology
  • Lactic Acid / pharmacokinetics
  • Monocarboxylic Acid Transporters / antagonists & inhibitors
  • Monocarboxylic Acid Transporters / metabolism*
  • Monocarboxylic Acid Transporters / physiology
  • Muscle Proteins / metabolism
  • Protein Isoforms / metabolism
  • RNA, Small Interfering / pharmacology
  • Sodium / pharmacology
  • Symporters / antagonists & inhibitors
  • Symporters / metabolism


  • Butyrates
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • Protein Isoforms
  • RNA, Small Interfering
  • SLC16A4 protein, human
  • SLC16A7 protein, human
  • Symporters
  • monocarboxylate transport protein 1
  • Lactic Acid
  • Sodium