Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells.
beta(2)-Adrenergic agonists stimulate ciliary beat frequency (CBF), an integral part of mucociliary clearance. To evaluate the differential effects of albuterol enantiomers and their racemic mixture on ciliary function, CBF and intracellular calcium were measured at room temperature from single ovine airway epithelial cells with use of digital videomicroscopy. Baseline CBF was 7.2 +/- 0.2 (SE) Hz (n = 80 measurements). R-albuterol (10 microM to 1 mM) stimulated CBF in a dose-dependent manner to maximally 24.4 +/- 5.4% above baseline. Racemic albuterol stimulated CBF to maximally 12.8 +/- 3.6% above baseline, a significantly lower increase compared with R-albuterol alone, despite identical R-enantiomer amounts in both groups. Simultaneous recordings of intracellular calcium concentration and CBF from single cells indicated that the CBF increase in response to R-albuterol was mediated through beta-receptors and stimulation of protein kinase A, in a calcium-dependent and -independent fashion. S-albuterol had a negligible effect on CBF and did not change intracellular calcium. Together, these results suggest that R-albuterol is more efficacious than racemic albuterol in stimulating CBF. Thus S-albuterol may interfere with the ability of R-albuterol to increase CBF.
Frohock
Jeffrey I
JI
Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine, Miami, Florida 33136, USA.
Wijkstrom-Frei
Corrine
C
Salathe
Matthias
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D011433:Propranolol / Q000494:pharmacology; D012756:Sheep; D013237:Stereoisomerism; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D017868:Cyclic AMP-Dependent Protein Kinases; D000420:Albuterol; D002118:Calcium