Glucocorticoids induce beta2-adrenergic receptor function in human nasal mucosa.
Glucocorticoids are hypothesized to induce beta2-adrenergic receptors (beta2-R) and their functions. The ability of dexamethasone (DEX) in vitro and beclomethasone dipropionate (BDP) in vivo to induce beta2-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 beta2-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 microM DEX, then challenged with media or 100 microM 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 beta2-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 beta2-R/beta-actin mRNA ratio (p < 0.05), and expression of beta2-R mRNA in glands. In vivo, BDP increased the beta2-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 beta2-R mRNA levels in vivo and in vitro, and can induce beta2-R function as assessed by submucosal gland exocytosis in vitro. While topical BDP induced epithelial beta2-R mRNA, it did not modulate exocytosis from the deeper submucosal glands.
Baraniuk
J N
JN
Environmental and Airway Disease Research Facility, University of Maryland, Baltimore, USA.
Ali
M
M
Brody
D
D
Maniscalco
J
J
Gaumond
E
E
Fitzgerald
T
T
Wong
G
G
Yuta
A
A
Mak
J C
JC
Barnes
P J
PJ
Bascom
R
R
Troost
T
T
D000287:Administration, Topical; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001985:Bronchial Provocation Tests; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D015854:Up-Regulation
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D000420:Albuterol