Purpose: The objective of this study was to investigate the role of organic cation transporters (OCT-2) in the uptake of small, hydrophilic molecules across the nasal epithelium. Immunohistochemistry studies performed previously confirm the presence of OCT-2 in the bovine respiratory and olfactory mucosa. Cimetidine, an OCT-2 substrate, was used as a model to evaluate the activity of this transporter in the olfactory and the respiratory tissues.

Methods: In vitro transport studies were carried out across excised nasal respiratory and olfactory mucosa in the mucosal to submucosal direction. Four different concentrations (0.2, 0.8, 4 and 20 mM) were studied, to evaluate the relationship between increasing concentration and flux. Additionally, the effect of an OCT2 inhibitor, pentamidine, on the flux of cimetidine across the nasal mucosa was also studied. An HPLC method was used to quantify cimetidine in the flux samples.

Results: The calibration curve obtained for cimetidine in buffer was found to be linear over a concentration range of 1 to 50 ng/mL with an r2=0.99. Transport studies showed that the flux of cimetidine increased linearly with increasing cimetidine concentrations. A saturation in flux was not observed in the concentration ranges studied. The addition of pentamidine, an OCT2 inhibitor, resulted in a decrease in the flux of cimetidine. These results demonstrate that OCT2 plays an important role in the uptake of cimetidine across the nasal mucosa.