THE EFFECTS OF SALMETEROL AND SALBUTAMOL ON CILIARY BEAT FREQUENCY OF CULTURED HUMAN BRONCHIAL EPITHELIAL-CELLS, INVITRO

Studies investigating mechanisms of mucociliary clearance have suggested that β2-adrenergic agents may significantly influence ciliary activity of epithelial cells and therefore play a vital role in the maintenance of functional integrity of the airways. We have cultured human bronchial epithelial cells, from surgical explants and investigated the effects of salbutamol and salmeterol, in a time- and dose-dependent manner, on the ciliary beat frequency (CBF) of these cells. Prior to and at several times after exposure to either salbutamol (10-8 to 10-3 m) or salmeterol (10-8 to 10-4 m), the epithelial cells were monitored for CBF and on the basis of data obtained from these studies, the effect of 10-6 m propranolol was investigated in the presence of optimal concentrations of salbutamol and salmeterol. Salbutamol was optimally active at a concentration of 10-4m and caused a transient but significant increase in the CBF from baseline level of 8.6 ± 0.4 to 9.6 ± 0.5 Hz (P < 0.05), after 2 h incubation. In contrast, salmeterol was maximally active at a concentration of 10-6m and caused a significantly rapid and prolonged increase in CBF from a baseline value of 9.2 ± 0.4 to 10.9 ± 0.6 Hz (P < 0.02) and 10.6 ± 0.8 Hz (P < 0.05) after 15 min and 24 h incubation, respectively. Propranolol (10-6 m) abrogated the salbutamol- but not the salmeterol-induced increases in CBF. Analysis of cultures for cAMP demonstrated that both salbutamol and salmeterol led to a significant release of cAMP into the culture medium and increased the amounts of CAMP from a baseline value of 4.5 ± 0.7 fmol/μg protein to 137.4 ± 38.7 and 151.8 ± 49.1 fmol/μg protein, respectively, after 24 h incubation (P < 0.001). Propranolol significantly attenuated both the salbutamol- and salmeterol-induced release of cAMP (P < 0.001 and P < 0.01, respectively). These results suggest that salmeterol may be of particular significance in the management of airway disease due to its role in mucociliary clearance, in addition to bronchodilation. © 1992.