Abstract
β-Adrenergic agonists are potent relaxing agents of airway smooth muscle; however, they are often incapable of fully reversing agonist-mediated contractions. The present study was designed to quantitate the relationship between β-adrenoceptor binding, signal transduction, and relaxation in rabbit tracheal smooth muscle (TSM). TSM segments contracted with acetylcholine to 25 to 75% maximal contraction were relaxed with cumulative administration of isoproterenol (ISO). A β-adrenergic receptor “deficit” was found, such that incomplete relaxation was achieved with full receptor occupancy. Binding studies with [3H]dihydroalprenolol demonstrated a β-adrenoceptor density of 33.1 ± 8.6 fmol/mg protein in control TSM. Paired studies were performed in TSM from rabbits treated with dexamethasone. Relative to control tissues, dexamethasone-treated TSM displayed twice as much relaxation and cAMP production in response to ISO and twice the β-adrenoceptor density (82.2 ± 12.3 fmol/mg protein). Dexamethasone did not affect Gi function, as assessed by the degree of functional antagonism exerted by acetylcholine on ISO-induced relaxations, or β-adrenoceptor-Gs coupling, as reflected in high-affinity β-agonist binding. Collectively, these results demonstrate that corticosteroid administration exerts parallel potentiating effects on β-adrenoceptor expression and function in rabbit airway smooth muscle.
Footnotes
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Send reprint requests to: Craig M. Schramm, M.D., Pediatric Pulmonary Division, Connecticut Children's Medical Center, 282 Washington St., Hartford, CT 06106. E-mail:cschram{at}ccmckids.org
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↵1 This research was sponsored by Grant HL-43285 from the National Heart, Lung, and Blood Institute of the National Institutes of Health and a Career Investigator Award from the American Lung Association and the American Lung Association of Connecticut.
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↵2 Some of these studies were performed in my laboratory at the Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine.
- Abbreviations:
- ACh
- acetylcholine
- TSM
- tracheal smooth muscle
- ISO
- isoproterenol
- DHA
- dihydroalprenolol
- Received June 21, 1999.
- Accepted September 17, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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