Transport of organic cations across human bronchial and bronchiolar epithelial barriers in vitro

In this study, we aimed to characterise the function of organic cation/carnitine transporters (OCT/Ns) in human bronchial (Calu‐ 3) and bronchiolar (H441) epithelial cells by using radiolabelled model substrates. The effect of time on uptake of [ 14 C]‐TEA (TEA) and [ 3 H]‐acetylcarnitine (Ac‐Car) was studied. In addition, bi‐directional transport studies were carried out. TEA uptake was found to be time‐dependent in both cell lines, however, H441 cells exhibited a higher level of uptake. Transport experments revealed net‐absorption of both compounds investigated. The apparent permeability coefficient ( P app ) for apical‐to‐basolateral transport was 1.93±0.03×10 −6 cm/s (TEA) and 1.36±0.01×10 −5 cm/s (Ac‐ Car) across Calu‐3 cells. The corresponding basolateral‐to‐apical values were 1.05±0.02×10 −6 cm/s (TEA) and 2.32±0.05×10 −6 cm/s (Ac‐Car), respectively. In the case of H441 cells, P app values for TEA were 2.09±0.03×10 −5 cm/s (a‐to‐b) and 8.99±0.06×10 −6 cm/s (b‐to‐a), and for Ac‐Car 2.71±0.02×10 −5 cm/s (a‐to‐b) and for Ac‐ Car 1.14±0.02×10 −5 (b‐to‐a), respectively. These data further support the hypothesis that organic cations are actively transported at the human air‐blood barrier, and that the involved transporter sites might play a role in processing of positively charged pharmaceuticals. This work is supported by SFI grant 07/SRC/B1154.