Allergen exposed primary human bronchial epithelial cells have inhibited transport of salbutamol sulphate only when functional organic cation tranporters are present

Background: Salbutamol sulphate (SS) is a short acting β2-agonist used to treat bronchospasm. House dust mite (HDM) is the most prevalent allergen associated with bronchospasm. Whether SS transports actively or passively across the airway epithelium is controversial and little is known about the effects of allergens on this transport.

Aims: To assess the effects of HDM on salbutamol sulphate transport across human primary bronchial epithelial cells (HBECs).

Methods: HBECs were cultured at an air-liquid interface (ALI) and apically treated (1H) with 50µg/ml HDM, 5mM triethylamine (TEA, an antagonist of organic cation transporters) or 6mM EGTA followed by 0.1mM SS. SS transport over 4 hours was assessed by HPLC. Barrier integrity was evaluated by fluorescein sodium(Flu-Na).

Results: Transport of SS in primary HBECs occurred through two different mechanisms. In around 50% of cells, TEA inhibited transport of SS from an apparent permeability (Papp) of 1.12×10-6 cm/s (SS alone) to 6.02×10-7 cm/s (SS+TEA), P<0.05, n=6) whilst in the other 50% of cells TEA was without effect (1.31×10-6 cm/s SS±TEA). Interestingly, only in the TEA sensitive cells, HDM stimulation inhibited the transport of SS (Papp 5.99×10-7 cm/s (n=6, p<0.05)). Flu-Na paracellular permeability was shown to be unaffected by HDM treatment. Destruction of tight junctions by EGTA increased SS transport.

Conclusions: SS flux occurs via either active absorption or passive diffusion. Furthermore, HDM affected active transport of SS suggesting that in the clinical scenario some patients may have impaired response to rescue medication when they are exposed to allergens.