Role for the A1 adenosine receptor in protecting against asthma
Jan 4, 2005 - 7:34:38 PM
Levels of the signaling molecule adenosine are increased in the lungs of asthmatics, and elevations of adenosine correlate with the degree of airway inflammation, suggesting that adenosine may play a provocative role in acute asthma attacks. Therefore much research has been focused on drugs that may potentially interact with known adenosine receptors the activation of which can have proinflammatory or anti-inflammatory effects, depending on the receptor type. Theophylline, the most widely prescribed drug for the treatment of airway disease worldwide, is able to block both pro- and anti-inflammatory actions of adenosine, potentially decreasing its efficiency. Researchers are now focused on determining the role of each adenosine receptor so that they may design drugs to interact with specific receptors and reduce airway inflammation.
As described in a report in the January 3 issue of the Journal of Clinical Investigation, Michael Blackburn led a team of researchers at the University of Texas Health Science Center and the National Institutes of Health to examine the role of the A1 adenosine receptor (A1AR) in a mouse model of lung injury and inflammation in which these mice possess elevated adenosine levels.
Blackburn et al. show that mice lacking A1AR die shortly after birth from severe inflammatory lung disease, indicating that A1AR serves an anti-inflammatory and thus protective role in the development of lung inflammation. The findings are particularly relevant in light of the fact that drugs that block A1AR are currently being investigated as a potential treatment for asthma.
In an accompanying commentary, Stephen Tilley and Richard Boucher from the University of North Carolina discuss this study and the potential clinical benefits of blocking A1 receptors in the airways of asthma patients.
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