beta-Adrenergic relaxation of rabbit tracheal smooth muscle: A receptor deficit that improves with corticosteroid administration

beta-Adrenergic agonists are potent relaxing agents of airway smooth muscle ; however, they are often incapable of fully reversing agonist-mediated con tractions. The present study was designed to quantitate the relationship be tween beta-adrenoceptor binding, signal transduction, and relaxation in rab bit tracheal smooth muscle (TSM). TSM segments contracted with acetylcholin e to 25 to 75% maximal contraction were relaxed with cumulative administrat ion of isoproterenol (ISO). A beta-adrenergic receptor "deficit" was found, such that incomplete relaxation was achieved with full receptor occupancy. Binding studies with [H-3] dihydroalprenolol demonstrated a beta-adrenocep tor 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 relaxati on and cAMP production in response to ISO and twice the beta-adrenoceptor d ensity (82.2 +/- 12.3 fmol/mg protein). Dexamethasone did not affect Gi fun ction, as assessed by the degree of functional antagonism exerted by acetyl choline on ISO-induced relaxations, or beta-adrenoceptor-G(s) coupling, as reflected in high-affinity beta-agonist binding. Collectively, these result s demonstrate that corticosteroid administration exerts parallel potentiati ng effects on beta-adrenoceptor expression and function in rabbit airway sm ooth muscle.