Details

Autor(en) / Beteiligte

• Brown, R A
• Spina, D
• Page, C P

Titel

Adenosine receptors and asthma

Ist Teil von

• British journal of pharmacology, 2008-03, Vol.153 (S1), p.S446-S456

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2008

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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 A1 receptor 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 A2A receptor is expressed on most inflammatory cells implicated in asthma, and as A2A stimulation activates adenylate cyclase and consequently elevates cAMP, selective A2A receptor agonists have now reached clinical development. However, initial reports concerning their efficacy are inconclusive. A2B receptor 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 A2B receptor 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 A3 receptor stimulation has been demonstrated to mediate inhibitory effects on eosinophils since it also elevates cAMP. However, some experimental reports suggest that A3 antagonists mediate anti‐inflammatory effects, thus the rationale for A3 receptor 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