Effects of albuterol isomers on the contraction and Ca2+ signaling of small airways in mouse lung slices.

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.