Adenosine receptors as promising therapeutic targets for drug development in chronic airway inflammation.
A growing body of evidence has emerged in support of a pro-inflammatory role for adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the airways such as asthma and COPD. The demonstration that adenosine enhances mast cell allergen-dependent activation, the notion that elevated levels of adenosine are present in chronically inflamed airways, and the results from exposure studies of nebulised adenosine showing dose-dependent bronchoconstriction in subjects with asthma and COPD, emphasise the importance of adenosine in the initiation, persistence and progression in these common inflammatory disorders of the airways. Adenosine exerts its manifold biological activities by interacting with at least four adenosine receptor subtypes. Selective activation or blockade of these sites is being exploited by the pharmaceutical industry in an attempt to generate novel therapies for asthma and COPD. This review article intends to address the potential role of adenosine in asthma and to put forward the idea that drugs that have been developed to selectively activate or downregulate adenosine receptor subtypes may constitute a considerable advance in the management of chronic airway inflammation.
Polosa
Riccardo
R
Dipartimento di Medicina Interna e Specialistica, Ascoli-Tomaselli Hospitals - University of Catania, Via Passo Gravina 187, 95125 Catania, Italy. polosa@unict.it
Holgate
Stephen T
ST
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D002908:Chronic Disease; D015195:Drug Design; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1