Moffatt, J.D., Lever, R. and Page, C.P. (2006) Activation of corticotropin-releasing factor receptor-2 causes bronchorelaxation and inhibits pulmonary inflammation in mice. FASEB Journal, 20 (11). p. 1877. 10.1096/fj.05-5315fje.
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ocortins are members of the corticotropin-releasing factor (CRF) family of peptides that bind to two receptors, CRF1 and CRF2. While CRF1 is a high-affinity receptor for CRF, urocortin III binds with much greater affinity to CRF2. In the present study we investigated the effect of CRF2 receptor activation with urocortin III on airway smooth muscle tone in vitro and in an acute model of airway inflammation in mice. Urocortin III caused relaxation of methacholine- precontracted mouse tracheal segments. CRF caused similar relaxation, but with reduced potency compared to urocortin III, consistent with the CRF2 receptor subtype. Relaxation induced by urocortin III was concentration- dependently inhibited by the CRF2 antagonist, astressin 2B, with an IC50 in the nanomolar range. These relaxations were potentiated by inhibition of phosphodiesterases but unaffected by inhibition of cyclooxygenase and NO or by removal of the epithelium. Finally, the number of neutrophils retrieved by bronchoalveolar lavage after administration of bacterial LPS (LPS) was reduced by prior intraperitoneal (i.p.) injection of urocortin III. This effect was also suppressed by astressin 2B, implicating CRF2 receptors. Therefore, CRF2 agonists appear to have both bronchorelaxant and anti-inflammatory activities and might represent an interesting therapeutic approach to the treatment of inflammatory lung diseases
|Uncontrolled Keywords:||Airway; Epithelium; Neutrophil; Smooth muscle; Urocortin|
|Departments, units and centres:||Department of Pharmacology > Department of Pharmacology|
|Journal or Publication Title:||FASEB Journal|
|Deposited By:||Library Staff|
|Deposited On:||10 May 2012 12:43|
|Last Modified:||10 May 2012 12:43|
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