Adenosine receptors and asthma

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Abstract
The accumulation of evidence implicating a role for adenosine in the pathogenesis of asthma has led to investigations into all adenosine receptor subtypes as potential therapeutic targets for the treatment of asthma. Selective A1receptor antagonists are currently in preclinical development since adenosine has been shown experimentally to mediate various features of asthma through this receptor such as bronchoconstriction, mucus secretion and inflammation. The A2Areceptor is expressed on most inflammatory cells implicated in asthma, and as A2Astimulation activates adenylate cyclase and consequently elevates cAMP, selective A2Areceptor agonists have now reached clinical development. However, initial reports concerning their efficacy are inconclusive. A2Breceptor antagonists are also under investigation based on the rationale that inhibiting the effects of adenosine on mast cells would be beneficial, in addition to other reported pro‐inflammatory effects mediated by the A2Breceptor on cells such as airway smooth muscle, epithelial cells and fibroblasts. Whilst the effects in pre‐clinical models are promising, their efficacy in the clinical setting has also yet to be reported. Finally, adenosine A3receptor stimulation has been demonstrated to mediate inhibitory effects on eosinophils since it also elevates cAMP. However, some experimental reports suggest that A3antagonists mediate anti‐inflammatory effects, thus the rationale for A3receptor ligands as therapeutic agents remains to be determined. In conclusion, establishing the precise role of adenosine in the pathogenesis of asthma and developing appropriate subtype selective agonists/antagonists represents an exciting opportunity for the development of novel therapeutics for the treatment of asthma.British Journal of Pharmacology(2008)153, S446–S456; doi:10.1038/bjp.2008.22

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