Glucocorticoids induce β2-adrenergic receptor function in human nasal mucosa

James N. Baraniuk, Mushtaq Ali, Daniel Brody, Jennifer Maniscalco, Ethan Gaumond, Thomas Fitzgerald, Godfrey Wong, Atsushi Yuta, Judith C.W. Mak, Peter J. Barnes, Rebecca Bascom, Thomas Troost

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)704-710
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume155
Issue number2
DOIs
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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