Suppression of inflammatory and immune responses by the A(2A) adenosine receptor: an introduction

The purine nucleoside adenosine has been described as a 'retaliatory metabolite' by virtue of its ability to function in an autocrine manner to modify the activity of a range of cell types following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by the binding of adenosine to any of four G-protein-coupled adenosine receptors. Most of the anti-inflammatory effects of adenosine have been assigned to the adenosine A(2A) receptor subtype, which is expressed in many immune and inflammatory cells. In this brief article, we will outline the growing evidence to support the hypothesis that the development of agonists selective for the A(2A) receptor is an effective strategy for suppressing the exaggerated inflammatory responses associated with many diseases by virtue of the receptor's ability to inhibit multiple pro-inflammatory signalling cascades.