Glucocorticoids induce beta(2)-adrenergic receptor function in human nasal mucosa

Glucocorticoids are hypothesized to induce beta(2)-adrenergic receptors (beta(2)-R) and their functions. The ability of dexamethasone (DEX) in vitro and beclomethasone dipropionate (BDP) in vivo to induce beta(2)-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 beta(2)-R-mediated glandula rexocytosis by glucocorticoids was proposed as an unambiguous outcome measure. Human nasal mucosa was cultured for 3 d with and without 1 mu M DEX, then challenged with media or 100 mu M 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 beta(2)-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, fn vitro, DEX treatment induced albuterol-mediated glandular exocytosis (p <0.04), and increased the steady-state beta(2)-R/beta-actin mRNA ratio (p <0.05), and expression of beta(2)-R mRNA in glands. In vive, BDP increased the beta(2)-R/beta-actin mRNA ratio in epithelial scrapings (p <0.04), but did not induce albuterol-mediated glandular secretion. We conclude that glucocorticoids increase steady-state beta(2)-R mRNA levels in vive and in vitro, and can induce beta(2)-R function as assessed by submucosal gland exocytosis in vitro. While topical BDP induced epithelial beta(2)-R mRNA, it did not modulate exocytosis from the deeper submucosal glands.