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Effect of adenosine A2A receptor activation in murine models of respiratory disorders.

Authors: Bonneau, O  Wyss, D  Ferretti, S  Blaydon, C  Stevenson, CS  Trifilieff, A 
Citation: Bonneau O, etal., Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L1036-43. Epub 2005 Dec 9.
Pubmed: (View Article at PubMed) PMID:16339780
DOI: Full-text: DOI:10.1152/ajplung.00422.2005

Activation of the adenosine A(2A) receptor has been postulated as a possible treatment for lung inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). In this report, we have studied the anti-inflammatory properties of the reference A(2A) agonist CGS-21680, given intranasally at doses of 10 and 100 microg/kg, in a variety of murine models of asthma and COPD. After an acute ovalbumin challenge of sensitized mice, prophylactic administration of CGS-21680 inhibited the bronchoalveolar lavage fluid inflammatory cell influx but not the airway hyperreactivity to aerosolized methacholine. After repeated ovalbumin challenges, CGS-21680 given therapeutically inhibited the bronchoalveolar lavage fluid inflammatory cell influx but had no effect on the allergen-induced bronchoconstriction, the airway hyperreactivity, or the bronchoalveolar lavage fluid mucin levels. As a comparator, budesonide given intranasally at doses of 0.1-1 mg/kg fully inhibited all the parameters measured in the latter model. In a lipopolysaccharide-driven model, CGS-21680 had no effect on the bronchoalveolar lavage fluid inflammatory cell influx or TNF-alpha, keratinocyte chemoattractant, and macrophage inflammatory protein-2 levels, but potently inhibited neutrophil activation, as measured by bronchoalveolar lavage fluid elastase levels. With the use of a cigarette smoke model of lung inflammation, CGS-21680 did not significantly inhibit bronchoalveolar lavage fluid neutrophil infiltration but reversed the cigarette smoke-induced decrease in macrophage number. Together, these results suggest that activation of the A(2A) receptor would have a beneficial effect by inhibiting inflammatory cell influx and downregulating inflammatory cell activation in asthma and COPD, respectively.

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CRRD Object Information
CRRD ID: 4890385
Created: 2010-12-15
Species: All species
Last Modified: 2010-12-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.