TY - JOUR T1 - (<em>S</em>)-Albuterol Increases Intracellular Free Calcium by Muscarinic Receptor Activation and a Phospholipase C-Dependent Mechanism in Airway Smooth Muscle JF - Molecular Pharmacology JO - Mol Pharmacol SP - 347 LP - 354 DO - 10.1124/mol.53.3.347 VL - 53 IS - 3 AU - Sankar Mitra AU - Mehmet Ugur AU - Ozlem Ugur AU - H. Maurice Goodman AU - John R. McCullough AU - Hiroshi Yamaguchi Y1 - 1998/03/01 UR - http://molpharm.aspetjournals.org/content/53/3/347.abstract N2 - Racemic albuterol has been one of the most widely used β2-adrenoceptor agonists for the relief of the symptoms of asthma, yet the use of β2 agonists has been known to induce bronchial hyperresponsiveness. To probe a possible role of theS-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 &gt;10 pm and 1 nm, respectively, with a maximal response by 150 and 100 nm, respectively. (S)-Albuterol (1 and 10 μm) induced Ca2+ oscillations, reaching 1–2 μm[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 nmatropine or 500 nm4-diphenylacetoxy-N-methylpiperidine but was insensitive to the β2 antagonist ICI 118,551 (10 μm). (S)-Albuterol (10 μm) increased inositol-1,4,5-trisphosphate levels by 213 ± 34.4% (p &lt; 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. ER -