Activation of corticotropin-releasing factor receptor-2 causes bronchorelaxation and inhibits pulmonary inflammation in mice

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.

Full text not available from this repository.

DOI: 10.1096/fj.05-5315fje

Abstract

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

Item Type:Article
Uncontrolled Keywords:Airway; Epithelium; Neutrophil; Smooth muscle; Urocortin
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:3185
Journal or Publication Title:FASEB Journal
Deposited By:Library Staff
Deposited On:10 May 2012 12:43
Last Modified:10 May 2012 12:43

Repository Staff Only: Item control page

School of Pharmacy Staff Only: Edit a copy to replace this item