Glucocorticoids induce β₂-adrenergic receptor function in human nasal mucosa

Glucocorticoids are hypothesized to induce β₂-adrenergic receptors (β₂-R) and their functions. The ability of dexamethasone (DEX) in vitro and beclomethasone dipropionate (BDP) in vivo to induce β₂-R messenger RNA (mRNA) and function was investigated in human nasal mucosa. In this tissue, albuterol does not stimulate exocytosis either in vivo or in vitro (Mullol and coworkers, 1992). Therefore, induction of β₂-R-mediated glandular exocytosis by glucocorticoids was proposed as an unambiguous outcome measure. Human nasal mucosa was cultured for 3 d with and without 1 μM DEX, then challenged with media or 100 μM albuterol. Culture supernatants were collected for measurement of exocytosed glandular products. Explant mRNA was extracted for reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ hybridization of β₂-R mRNA performed. In vivo, normal subjects received saline or BDP for 3 d before albuterol nasal provocation. Concentrations of exocytosed products were measured in nasal secretions. RNA was extracted from nasal epithelial scrapings for RT-PCR. In vitro, DEX treatment induced albuterol-mediated glandular exocytosis (p < 0.04), and increased the steady-state β₂-R/β-actin mRNA ratio (p < 0.05), and expression of β₂-R mRNA in glands. In vivo, BDP increased the β₂-R/β- actin mRNA ratio in epithelial scrapings (p < 0.04), but did not induce albuterol-mediated glandular secretion. We conclude that glucocorticoids increase steady-state β₂-R mRNA levels in vivo and in vitro, and can induce β₂-R function as assessed by submucosal gland exocytosis in vitro. While topical BDP induced epithelial β₂-R mRNA, it did not modulate exocytosis from the deeper submucosal glands.