Organic cation transporters in human nasal primary culture: expression and functional activity

Ther Deliv. 2013 Apr;4(4):439-51. doi: 10.4155/tde.13.10.

Abstract

Background: The majority of drugs cross epithelial cells by either passive diffusion or via carrier-mediated drug transporters. The aim of this study was to investigate the transport characteristics, protein expression and localization of organic cation transporters in human nasal epithelium.

Methods & results: The expression, localization and transport characteristics of the transporters were investigated using permeation, PCR and immunohistochemistry. The uptake of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide followed Michaelis-Menten kinetics. Its intracellular accumulation of the compound was inhibited by organic cation transporters (OCTs) and carnitine/organic cation transporter (OCTNs) inhibitors. Detected OCT1-3, OCTN1 and OCTN2 gene transcripts correlated with immunohistological staining for OCT1-3, OCTN1 and OCTN2 antibodies. Except for OCTN1, the antibodies were generally localized on the apical side of the epithelial cells.

Conclusion: Based on the immunohistochemical and uptake/transport studies, we conclude that the human nasal epithelium expresses OCT1-3, OCTN1 and OCTN2 transporters mainly on the apical side of the nasal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Membrane Permeability*
  • Cell Polarity
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Fluorescent Dyes / metabolism
  • Humans
  • Immunohistochemistry
  • Kinetics
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism*
  • Organic Anion Transporters, Sodium-Independent / metabolism
  • Organic Cation Transport Proteins / antagonists & inhibitors
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism*
  • Organic Cation Transporter 1 / metabolism
  • Organic Cation Transporter 2
  • Primary Cell Culture
  • Reverse Transcriptase Polymerase Chain Reaction
  • Solute Carrier Family 22 Member 5
  • Symporters

Substances

  • Fluorescent Dyes
  • Organic Anion Transporters, Sodium-Independent
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 1
  • Organic Cation Transporter 2
  • SLC22A2 protein, human
  • SLC22A4 protein, human
  • SLC22A5 protein, human
  • Solute Carrier Family 22 Member 5
  • Symporters
  • organic anion transport protein 3