Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin.
1. Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. 2. We have investigated the effect of salmeterol, a long-acting beta 2-adrenoceptor agonist, on pyocyanin-induced slowing of human CBF in vitro. Salmeterol (2 x 10(-7) M) was found to reduce pyocycanin (20 micrograms ml-1)-induced slowing of CBF by 53% and the fall in intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) by 26% and ATP by 29%. 3. Another beta 2-adrenoceptor agonist, isoprenaline (2 x 10(-7) M), also inhibited pyocyanin-induced slowing of CBF by 39%. 4. The effects of salmeterol (30 min preincubation) persisted after washing the cells. 5. Propranolol (10(-7) M) and the beta 2-specific antagonist, ICI 118551 (10(-6) M) blocked the protective 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 stimulation of beta 2-adrenoceptors. 6. Pyocyanin-induced ciliary slowing is associated with a substantial fall in intracellular cyclic AMP and ATP. Salmeterol reversed the effects of pyocyanin on cyclic AMP and ATP. 7. Mucociliary clearance is an important defence mechanism of the airways against bacterial infection. Salmeterol may benefit patients colonized by P. aeruginosa, not only by its bronchodilator action, but also by protecting epithelial cells from pyocyanin-induced slowing of CBF.
Kanthakumar
K
K
Department of Thoracic Medicine, Royal Brompton National Heart and Lung Institute, London.
Cundell
D R
DR
Johnson
M
M
Wills
P J
PJ
Taylor
G W
GW
Cole
P J
PJ
Wilson
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009079:Mucociliary Clearance / Q000187:drug effects*; D009297:Nasal Mucosa / Q000166:cytology* / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D011710:Pyocyanine / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D000255:Adenosine Triphosphate; D011710:Pyocyanine; D000242:Cyclic AMP; D007545:Isoproterenol; D000420:Albuterol