Therapeutic targeting of adenosine receptors in inflammatory diseases

Adenosine, an endogenous nucleoside that is ubiquitous in many mammalian cell types, has been shown to regulate a number of physiological properties. The mechanism by which adenosine exerts its activity is via cell surface receptors. Following the identification and subsequent cloning of a series of adenosine receptors over the past 15 years, an explosion of information regarding their role in mediating adenosine effects has occurred. To date, four adenosine receptors have been identified by both pharmacological and molecular studies. These receptors are subtyped as the A1, A2A, A2B and A3 receptors, each of which has been ascribed a number of cellular physiological properties. Early research suggested that adenosine, functioning via these cell surface receptors, may mediate anti-inflammatory effects. As a result, more recent studies have examined the role of adenosine receptors in regulating inflammatory states using both in vitro and in vivo strategies. Despite the complex nature of adenosine receptor regulation of inflammatory states identified thus far, research in this area is likely to identify key mechanisms to be targeted for successful intervention. The purpose of this review is to characterise the potential of utilising adenosine receptor signalling as therapeutic targets in inflammatory disease states.