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Inhibition by salbutamol of the proliferation of human airway smooth muscle cells grown in culture
Author(s) -
Tomlinson Paul R.,
Wilson John W.,
Stewart Alastair G.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14784.x
Subject(s) - salbutamol , propranolol , antagonist , endocrinology , medicine , pharmacology , chemistry , cell growth , biology , receptor , biochemistry , asthma
1 β 2 ‐Adrenoceptor agonists may exacerbate asthma by reducing the release of the anti‐proliferative and anti‐inflammatory molecule, heparin from mast cells in the airway. In this study, the direct effects of the clinically used bronchodilator, salbutamol, on the proliferation of airway smooth muscle cells grown in culture and stimulated with a range of mitogens have been examined. 2 In mitogen‐stimulated cells, salbutamol (0.1–100 n m ) inhibited [ 3 H]‐thymidine incorporation in a concentration‐dependent manner. Salbutamol (100 n m ) pretreatment reduced the mitogenic responses to thrombin (0.3 u ml −1 ), epidermal growth factor (EGF) (300 p m ) and U46619 (100 n m ) by 61.7 ± 6.1%, 46.9 ± 13.9% and 57.6 ± 12.7%, respectively. However, salbutamol pretreatment did not appear to reduce the small mitogenic response to endothelin‐1. 3 Increases in [ 3 H]‐leucine incorporation in thrombin (0.3 u ml −1 )‐stimulated cells were reduced by salbutamol (100 n m ) by 27.7 ± 2.8%. Similarly, thrombin (0.3 u ml −1 )‐stimulated increases in cell number were also inhibited by salbutamol (100 n m ) pretreatment. Thus, the effect of salbutamol in decreasing thrombin‐induced [ 3 H]‐leucine incorporation may, at least in part, be explained by inhibition of cell proliferation. 4 The inhibition of cell proliferation by salbutamol was prevented by pretreatment with either the non‐selective β‐adrenoceptor antagonist, propranolol (0.3 μ m ) or the selective β 2 ‐adrenoceptor antagonist, ICI 118551 (50 n m ). 5 These results indicate that salbutamol, through activation of a β 2 ‐adrenoceptor, has a direct inhibitory effect on proliferation elicited by the mitogens thrombin, EGF, and U46619. Thus, it seems likely that this direct inhibitory action of β 2 ‐adrenoceptor agonists would override any indirect action to accelerate airway smooth muscle proliferation. These observations lead us to suggest that β 2 ‐adrenoceptor agonists exacerbate asthma by mechanisms unrelated to airway smooth muscle proliferation.