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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.
Acknowledgments
The authors thank C Wyse for liaison between QEII hospital and our laboratory, and K Goralski for PCR instrumentation.
Financial & competing interests disclosure
This project was funded with a grant from the Dalhousie University Pharmacy Endowment Fund. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.