Dexamethasone potentiates high-affinity β-agonist binding and Gsα protein expression in airway smooth muscle

Corticosteroids enhance P-adrenergic responses by actions at both P-adrenoceptor (P-AR) and post-p-AR sites. The present study investigated the effects of dexamethasone on P-AR density, high-affinity P-agonist binding, G(s)alpha and G(i)alpha protein expression, and cAMP responses in bovine tracheal smooth muscle (bTSM). Dexamethasone treatment of cultured bTSM cells increased total beta-AR density 1.6- to 1.9-fold as assessed by the saturation binding of [H-3]CGP-12177 and by displacement of radioligand binding with isoproterenol. Isoproterenol bound to the 6-AR at two sites, a high-affinity site with a density of 5.9 +/- 1.2 fmol/mg protein and a low-affinity site with a density of 16.9 +/- 1.0 fmol/mg protein. Dexamethasone increased both high- and low-affinity isoproterenol binding sites to 11.1 +/- 2.2 and 25.9 +/- 2.1 fmol/mg protein, respectively, without influencing agonist binding affinities. Dexamethasone also selectively increased G(s)alpha protein levels from 0.99 +/- 0.14 to 1.46 +/- 0.17 mu g/mg protein without affecting G(i)alpha levels. The net effect of these changes was a 1.8-fold increase in maximal isoproterenol-induced cAMP generation in dexamethasone-treated bTSM cells. These findings provide new insights into the corticosteroid regulation of P-adrenergic signaling pathways in airway smooth muscle.