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Vol. 53, Issue 3, 347-354, March 1998
Department of Physiology (S.M., M.U., O.U., H.M.G., H.Y.),
University of Massachusetts Medical School, Worcester, Massachusetts
01655, and
Sepracor, Inc. (J.R.M.), Marlborough, Massachusetts 01752
Racemic albuterol has been one of the most widely used
2-adrenoceptor agonists for the relief of the symptoms
of asthma, yet the use of 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 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 nM
atropine or 500 nM
4-diphenylacetoxy-N-methylpiperidine but was insensitive
to the 2 antagonist ICI 118,551 (10 µM). (S)-Albuterol (10 µM) 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.
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