Young P G, Skinner S J, Black P N
Department of Paediatrics, University of Auckland School of Medicine, Auckland Hospital, New Zealand.
Eur J Pharmacol. 1995 Jan 24;273(1-2):137-43. doi: 10.1016/0014-2999(94)00679-2.
An increase in airway smooth muscle is a characteristic feature of asthma. Because beta-adrenoceptor agonists and corticosteroids are commonly used in the treatment of asthma we have studied the effects of these medicines on the growth of airway smooth muscle. These agents were incubated with bovine airway smooth muscle cells for 40 h for measurement of thymidine incorporation and 64 h for measurement of cell counts. Salbutamol inhibited thymidine incorporation (IC50 = 60 nM) and led to a reduction in cell number (IC50 = 10 nM). At 10 microM there was a 14.6 +/- 2.6% reduction in cell number. Salmeterol also inhibited the growth of the airway smooth muscle cells but the effect did not plateau at 10 microM. At this concentration there was an 89.5 +/- 3.6% reduction in thymidine incorporation and a 44.1 +/- 5.2% reduction in cell number. Cortisol and beclomethasone dipropionate were more potent than salbutamol in inhibiting thymidine incorporation with IC50 values of 5 nM and 0.2 nM respectively. Cortisol 100 nM led to a 16.6 +/- 6.5% reduction and beclomethasone dipropionate 3 nM led to a 17.8 +/- 5.8% reduction in cell number. If similar effects occur in man and in vivo, these medicines could act directly on airway smooth muscle to inhibit the development of hyperplasia.
气道平滑肌增生是哮喘的一个特征性表现。由于β-肾上腺素能受体激动剂和皮质类固醇常用于哮喘治疗，我们研究了这些药物对气道平滑肌生长的影响。将这些药物与牛气道平滑肌细胞孵育40小时以测量胸苷掺入量，孵育64小时以测量细胞计数。沙丁胺醇抑制胸苷掺入（IC50 = 60 nM）并导致细胞数量减少（IC50 = 10 nM）。在10μM时，细胞数量减少了14.6±2.6%。沙美特罗也抑制气道平滑肌细胞的生长，但在10μM时作用未达到平台期。在此浓度下，胸苷掺入减少了89.5±3.6%，细胞数量减少了44.1±5.2%。皮质醇和二丙酸倍氯米松在抑制胸苷掺入方面比沙丁胺醇更有效，IC50值分别为5 nM和0.2 nM。100 nM的皮质醇使细胞数量减少了16.6±6.5%，3 nM的二丙酸倍氯米松使细胞数量减少了17.8±5.8%。如果在人体和体内出现类似作用，这些药物可能直接作用于气道平滑肌以抑制增生的发展。
