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beta-adrenergic relaxation of rabbit tracheal smooth muscle: a receptor deficit that improves with corticosteroid administration.

Authors :
Schramm CM
Source :
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2000 Jan; Vol. 292 (1), pp. 280-7.
Publication Year :
2000

Abstract

beta-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 beta-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 beta-adrenergic receptor "deficit" was found, such that incomplete relaxation was achieved with full receptor occupancy. Binding studies with [(3)H]dihydroalprenolol demonstrated a beta-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 beta-adrenoceptor density (82.2 +/- 12.3 fmol/mg protein). Dexamethasone did not affect G(i) function, as assessed by the degree of functional antagonism exerted by acetylcholine on ISO-induced relaxations, or beta-adrenoceptor-G(s) coupling, as reflected in high-affinity beta-agonist binding. Collectively, these results demonstrate that corticosteroid administration exerts parallel potentiating effects on beta-adrenoceptor expression and function in rabbit airway smooth muscle.

Details

Language :
English
ISSN :
0022-3565
Volume :
292
Issue :
1
Database :
MEDLINE
Journal :
The Journal of pharmacology and experimental therapeutics
Publication Type :
Academic Journal
Accession number :
10604959