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 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.
Schramm
C M
CM
Pediatric Pulmonary Division, University of Connecticut School of Medicine, Farmington, CT 06106, USA. cschramccmkids.org
D000109:Acetylcholine / Q000494:pharmacology; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004082:Dihydroalprenolol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011485:Protein Binding; D011817:Rabbits; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D004082:Dihydroalprenolol; D003907:Dexamethasone; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007545:Isoproterenol; D000109:Acetylcholine