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D73. RECEPTOR INPUT OF AIRWAY NETWORKING - Synergistic Enhancement Of Glucocorticoid-Dependent Transcription By Epinephrine In The Presence Of Dexamethasone Is Predominantly Mediated Through The 22-Adrenoceptor by Gaunt, David D.; Giembycz, Mark; Johnson, David W.; Newton, Robert is a scholarly article available to read on EtoBox.

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RATIONALE: Glucocorticoid/long-acting β -adrenoceptor agonist combinations are invaluable in the treatment of COPD and asthma due 2 to their clinically observed synergistic benefits. Equally, treatment with dexamethasone, a synthetic glucocorticoid, plus epinephrine, a non-selective adrenoceptor agonist, significantly reduced admissions in children presenting at emergency departments with acute bronchiolitis. The current study has therefore evaluated the role of adrenoceptor subtypes in the enhancement of glucocorticoid-dependent transcription by adrenaline. METHODS: Real-time PCR was carried out using a TaqMan gene array. Glucocorticoid receptor (GR)-and PKA-dependent transcription was modeled using simple 2× glucocorticoid response element (GRE)-or 6x cAMP response element (CRE)-dependent luciferase reporters in human bronchial epithelial BEAS-2B cells. Cells were incubated with antagonists for 30 min before stimulation with dexamethasone and/or adrenoceptor agonists. After 6 h, cells were harvested for luciferase assay. Signalling from Gq-coupled GPCRs was monitored by loading BEAS-2B cells with the calcium sensitive dye, Fluo4 NW. Expression of RGS2 was evaluated by western blo

Author

Gaunt, David D.; Giembycz, Mark; Johnson, David W.; Newton, Robert

Publisher

American Thoracic Society

Published

2012

Language

EN