EFFECT OF SALMETEROL ON HUMAN NASAL EPITHELIAL-CELL CILIARY BEATING -INHIBITION OF THE CILIOTOXIN, PYOCYANIN

1 Patients with airway infection by Pseudomonas aeruginosa have impair ed mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, s lows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. 2 We have investigated the effec t of salmeterol, a long-acting beta(2)-adrenoceptor agonist, on pyocya nin-induced slowing of human CBF in vitro. Salmeterol (2 x 10(-7) M) w as found to reduce pyocycanin (20 mu g ml(-1))-induced slowing of CBF by 53% and the fall in intracellular adenosine 3':5'-cyclic monophosph ate (cyclic AMP) by 26% and ATP by 29%. 3 Another beta(2)-adrenoceptor agonist, isoprenaline (2 x 10(-7) M), also inhibited pyocyanin-induce d slowing of CBF by 39%. 4 The effects of salmeterol (30 min preincuba tion) persisted after washing the cells. 5 Propranolol (10(-7) M) and the beta(2)-specific antagonist, ICI 118551 (10(-6) M) blocked the pro tective effects of salmeterol completely, but atenolol (10(-6) M) was less effective. These results suggested that the effects of salmeterol on pyocyanin-induced effects were mediated primarily via the stimulat ion of beta(2)-adrenoceptors. 6 Pyocyanin-induced ciliary slowing is a ssociated with a substantial fall in intracellular cyclic AMP and ATP. Salmeterol reversed the effects of pyocyainin on cyclic AMP and ATP. 7 Mucociliary clearance is an important defence mechanism of the airwa ys against bacterial infection. Salmeterol may benefit patients coloni zed by P. aeruginosa, not only by its bronchodilator action, but also by protecting epithelial cells from pyocyanin-induced slowing of CBF.