| Abstrakt: |
Adenosine signaling has been implicated in the exacerbation of chronic inflammatory lung diseases such as asthma. Challenging the airways with adenosine leads to bronchoconstriction; however, little is known about the role of endogenous adenosine on airway physiology. We examined the consequences of chronic adenosine elevations in mice genetically manipulated to contain low levels of the purine catabolic enzyme adenosine deaminase (ADA), which controls adenosine concentrations in tissues and cells. Examination of airway physiology in these animals revealed an increase in airway responsiveness. This increase in airway responsiveness was dependent on elevated adenosine in that treatment with ADA enzyme therapy reversed increased airway responsiveness in conjunction with lowering lung adenosine levels. Treatment with the broad‐spectrum adenosine receptor antagonist theophylline prevented airway hyperresponsiveness, implicating the involvement of adenosine receptors. Furthermore, transcript levels for the A1, A2B, and A3adenosine receptors were elevated in the lungs of ADA‐deficient mice. These findings suggest that endogenous increases in lung adenosine concentrations are associated with alterations in airway physiology. Drug Dev. Res. 58:472–478, 2003. © 2003 Wiley‐Liss, Inc. |
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