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The β[sub 2]-adrenergic receptor (β[sub 2]AR) signal transduction system regulates many key functions of airway epithelium. In this study, we have pharmacologically characterized the β[sub 2]AR and determined the impact of glucocorticoids on β[sub 2]AR gene transcription in SPOC1 cells, a continuous cell line derived from the tracheal epithelium of rats. [[sup 125]I] Cyanoiodopindolol assays demonstrated that binding to SPOC1 cell membranes was saturable (B[sub max] = 62.6 ± 6fmol/mg protein) and of high affinity (K[sub d] = 6.3 ± 0.8pM). From competition experiments, the rank order of potency of agonists (isoproterenol > epinephrine norepinephrine) and the high affinity (K[sub i] = 0.37 ± 0.05nM) of the β[sub 2]-selective antagonist ICI 118, 551 suggested the predominance of the β[sub 2]AR subtype. Two isoforms of the α subunit of G[sub s] (45 and 52 kDa) were identified by Western blot analysis. Isoproterenol-stimulated cyclic AMP levels increased in a dose-dependent manner, confirming that SPOC1 cell β[sub 2]ARs are functionally coupled to adenylyl cyclase. The effect of glucocorticoids on β[sub 2]AR expression was assessed in radioligand and transient transfection assays. Dexamethasone treatment of SPOC1 cells increased both β[sub 2]AR protein and β[sub 2]AR-luciferase fusion gene expression 1.6- to 3.1-fold, with the greatest increase demonstrated in cells cultured at low density compared to cells grown at high density. [ABSTRACT FROM AUTHOR]