Glucocorticoids induce beta2-adrenergic receptor function in human nasal mucosa

Area of Science:

• Pharmacology
• Molecular Biology
• Respiratory Medicine

Background:

• Glucocorticoids are hypothesized to upregulate beta2-adrenergic receptors (beta2-R) and their functions.
• Human nasal mucosa beta2-R function, specifically glandular exocytosis, is a potential outcome measure for glucocorticoid effects.

Purpose of the Study:

• To investigate the ability of dexamethasone (DEX) in vitro and beclomethasone dipropionate (BDP) in vivo to induce beta2-R messenger RNA (mRNA) and function in human nasal mucosa.
• To assess beta2-R-mediated glandular exocytosis as an outcome measure for glucocorticoid effects.

Main Methods:

• Human nasal mucosa cultured with DEX and challenged with albuterol to measure exocytosis and beta2-R mRNA via RT-PCR and in situ hybridization.
• In vivo study involving subjects receiving BDP or saline, followed by albuterol nasal provocation to measure exocytosed products and epithelial beta2-R mRNA via RT-PCR.

Main Results:

• In vitro, DEX induced albuterol-mediated glandular exocytosis (p < 0.04) and increased beta2-R/beta-actin mRNA ratio (p < 0.05).
• In vivo, BDP increased epithelial beta2-R/beta-actin mRNA ratio (p < 0.04) but did not induce albuterol-mediated glandular secretion.
• Glucocorticoids increase steady-state beta2-R mRNA levels in vivo and in vitro.

Conclusions:

• Glucocorticoids can induce beta2-R function, specifically submucosal gland exocytosis, in vitro.
• Topical BDP increased epithelial beta2-R mRNA in vivo but did not affect exocytosis from deeper submucosal glands.