Frohock Jeffrey I, Wijkstrom-Frei Corrine, Salathe Matthias
Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine, Miami, Florida 33136, USA.
J Appl Physiol (1985). 2002 Jun;92(6):2396-402. doi: 10.1152/japplphysiol.00755.2001.
beta(2)-Adrenergic agonists stimulate ciliary beat frequency (CBF), an integral part of mucociliary clearance. To evaluate the differential effects of albuterol enantiomers and their racemic mixture on ciliary function, CBF and intracellular calcium were measured at room temperature from single ovine airway epithelial cells with use of digital videomicroscopy. Baseline CBF was 7.2 +/- 0.2 (SE) Hz (n = 80 measurements). R-albuterol (10 microM to 1 mM) stimulated CBF in a dose-dependent manner to maximally 24.4 +/- 5.4% above baseline. Racemic albuterol stimulated CBF to maximally 12.8 +/- 3.6% above baseline, a significantly lower increase compared with R-albuterol alone, despite identical R-enantiomer amounts in both groups. Simultaneous recordings of intracellular calcium concentration and CBF from single cells indicated that the CBF increase in response to R-albuterol was mediated through beta-receptors and stimulation of protein kinase A, in a calcium-dependent and -independent fashion. S-albuterol had a negligible effect on CBF and did not change intracellular calcium. Together, these results suggest that R-albuterol is more efficacious than racemic albuterol in stimulating CBF. Thus S-albuterol may interfere with the ability of R-albuterol to increase CBF.
β₂肾上腺素能激动剂可刺激纤毛摆动频率（CBF），这是黏液纤毛清除功能的一个重要组成部分。为评估沙丁胺醇对映体及其外消旋混合物对纤毛功能的不同影响，在室温下，使用数字视频显微镜从单个绵羊气道上皮细胞中测量了CBF和细胞内钙。基线CBF为7.2±0.2（SE）Hz（n = 80次测量）。R-沙丁胺醇（10μM至1 mM）以剂量依赖性方式刺激CBF，最大增幅比基线高24.4±5.4%。外消旋沙丁胺醇刺激CBF最大增幅比基线高12.8±3.6%，尽管两组中的R-对映体含量相同，但与单独使用R-沙丁胺醇相比，增幅明显较低。对单个细胞同时记录细胞内钙浓度和CBF表明，R-沙丁胺醇引起的CBF增加是通过β受体和蛋白激酶A的刺激介导的，呈钙依赖性和非依赖性方式。S-沙丁胺醇对CBF的影响可忽略不计，且不改变细胞内钙。总之，这些结果表明，R-沙丁胺醇在刺激CBF方面比外消旋沙丁胺醇更有效。因此，S-沙丁胺醇可能会干扰R-沙丁胺醇增加CBF的能力。
