Adenosine receptors and the control of endothelial cell function in inflammatory disease

The nucleoside adenosine accumulates in many tissues following the onset of ischaemia and inflammation. This initiates a series of protective mechanisms in target cells upon binding and activation of a family of four G-protein-coupled cell surface adenosine receptor (AR) proteins. The magnitude and duration of adenosine's effects are dictated by the identity and expression levels of each receptor subtype on individual cell types within the hypoxic microenvironment. Given the key role of endothelial cells (ECs) in the development of inflammatory diseases, such as sepsis, rheumatoid arthritis (RA) and atherosclerosis, ARs represent attractive targets for therapeutic intervention in these conditions. In this review, we examine several critical aspects of endothelial function in vivo, assess the role of individual AR subtypes in these events and, where known, discuss the molecular mechanisms by which specific ARs exert their effects.