Drug specificity and intestinal membrane localization of human organic cation transporters (OCT)

Biochem Pharmacol. 2005 Dec 5;70(12):1851-60. doi: 10.1016/j.bcp.2005.09.011. Epub 2005 Nov 2.


This study was performed to investigate which human organic cation transporter, hOCT1, hOCT2 or hOCT3, participates with regard to cation specificity and membrane localization in the intestinal absorption of orally available cationic drugs. Inhibition of N-[methyl-3H]4-phenylpyridinium ([3H]MPP+) uptake by various compounds into Caco-2 cells and into cells (HEK-293 or CHO) that were stably transfected with hOCT1, hOCT2 or hOCT3 was compared. The uptake of [3H]MPP+ into Caco-2 cells was inhibited by atropine, butylscopolamine, clonidine, diphenhydramine, etilefrine, quinine and ranitidine with IC50 values between 6 microM and 4 mM. Transepithelial, apical to basal flux of [3H]MPP+ across Caco-2 cell monolayers was also strongly inhibited by these compounds. The inhibitory potency of the cationic drugs and prototypical organic cations at Caco-2 cells correlated well with the inhibitory potency measured at CHO-hOCT3 cells but much less with that at HEK-hOCT1 and -hOCT2 cells. This is functional evidence for the predominant role of hOCT3. Etilefrine and atropine were specifically transported into CHO cells by hOCT3. In Caco-2 cells, the mRNA of all three hOCT and the proteins hOCT2 and hOCT3 were detected. More importantly, immunocytochemical analyses of human jejunum revealed for the first time that hOCT3 is localized to the brush border membrane whereas hOCT1 immunolabeling was mainly observed at the lateral membranes of the enterocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacokinetics
  • Amino Acid Sequence
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Cell Membrane / chemistry
  • Humans
  • Intestines / chemistry*
  • Molecular Sequence Data
  • Octamer Transcription Factor-1 / analysis*
  • Octamer Transcription Factor-1 / physiology
  • Organic Cation Transport Proteins / analysis*
  • Organic Cation Transport Proteins / physiology
  • Organic Cation Transporter 2
  • Transfection


  • Octamer Transcription Factor-1
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • POU2F1 protein, human
  • SLC22A2 protein, human
  • solute carrier family 22 (organic cation transporter), member 3
  • 1-Methyl-4-phenylpyridinium