Effects of albuterol isomers on the contraction and Ca2+ signaling of small airways in mouse lung slices
Department of Physiology
Albuterol; Animals; Bronchi; Bronchoconstriction; Bronchodilator Agents; Calcium Signaling; Lung; Mice; Mice, Inbred BALB C; Organ Culture Techniques; Stereoisomerism
Life Sciences | Medicine and Health Sciences
The beta(2)-adrenergic agonist, albuterol, is used as a bronchodilator by patients with asthma and consists of a racemic mixture of (R)- and (S)-albuterol. However, the action of the individual enantiomers is poorly understood. Consequently, we investigated the effects of (R)-, (S)- and racemic-albuterol on airway smooth muscle cell (SMC) contraction and Ca(2+) signaling in mouse lung slices with phase-contrast and confocal microscopy. (R)-albuterol relaxed airways contracted with methacholine (MCh) in a dose-dependent manner. By contrast, (S)-albuterol had no effect on airways. (R)-albuterol had a greater relaxant effect than a double concentration of racemic albuterol. Because MCh-induced contraction of airway SMCs is mediated by Ca(2+) oscillations and an increase in Ca(2+) sensitivity, the effects of albuterol on these responses were examined. Both (R)- and racemic albuterol decreased the frequency of the MCh-induced Ca(2+) oscillations by a similar amount. However, (R)-albuterol was more effective than racemic albuterol in decreasing the Ca(2+) sensitivity of the airway SMCs in "model" lung slices with a clamped [Ca(2+)](i). In contrast, (S)-albuterol had no effect on the Ca(2+) oscillations or the Ca(2+) sensitivity. In conclusion, (R)-albuterol consistently induced a greater airway relaxation than racemic albuterol, and (S)-albuterol appears to be responsible for this reduced efficacy.
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Citation: Am J Respir Cell Mol Biol. 2008 May;38(5):524-31. Epub 2007 Dec 6. Link to article on publisher's site
DOI of Published Version
American journal of respiratory cell and molecular biology
Delmotte, Philippe and Sanderson, Michael J., "Effects of albuterol isomers on the contraction and Ca2+ signaling of small airways in mouse lung slices" (2007). Open Access Articles. 1925.