The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro.
Studies investigating mechanisms of mucociliary clearance have suggested that beta 2-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(-4) M 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(-6) M 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Respiratory Medicine, St Bartholomew's Hospital, London, UK.
J L
JL
Devalia
R J
RJ
Sapsford
C
C
Rusznak
M J
MJ
Toumbis
R J
RJ
Davies
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D011433:Propranolol / Q000494:pharmacology; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000068299:Salmeterol Xinafoate; D011433:Propranolol; D000420:Albuterol