Akademik Veri Yönetim Sistemi
MOLECULAR PHARMACOLOGY, cilt.53, sa.3, ss.347-354, 1998 (SCI-Expanded)
Racemic albuterol has been one of the most widely used beta(2)-adrenoceptor agonists for the relief of the symptoms of asthma, yet the use of beta(2) agonists has been known to induce bronchial hyperresponsiveness. To probe a possible role of the S-enantiomer for hyperresponsiveness, we determined the effects of (S)-albuterol on intracellular Ca2+ concentration ([Ca2+](i)) in dissociated bovine tracheal smooth muscle cells. Both (S)-and (R,S)-albuterol increased [Ca2+](i) at concentrations of >10 pM and 1 nM, respectively, with a maximal response by 150 and 100 nM, respectively. (S)-Albuterol (1 and 10 mu M) induced Ca2+ oscillations, reaching 1-2 mu M [Ca2+](i). This response is in a stark contrast to that of (R)-albuterol, which decreased [Ca2+](i). The increase in [Ca2+](i) was blocked by 100 nM atropine or 500 nM 4-diphenylacetoxy-N-methylpiperidine but was insensitive to the beta(2), antagonist ICI 118,551 (10 mu M). (S)-Albuterol (10 mu M) increased inositol-1,4,5-trisphosphate levels by 213 +/- 34.4% (p < 0.05, four experiments) in cells exposed for 30 sec. The sustained phase of the Ca2+ increase was absent in Ca2+-free solution, suggesting that Ca2+ influx was responsible for the sustained Ca2+ response. The results also suggest that (S)-albuterol may cross-react with muscarinic receptors. As a Ca2+ agonist in airway smooth muscle, (S)-albuterol may have profound clinical implications because 50% of prescribed racemic albuterol is composed of (S)-albuterol.