Importance of the field: Ischemia–reperfusion (IR) injury is a common problem after transplantation as well as myocardial infarction and stroke. IR initiates an inflammatory response leading to rapid tissue damage. Adenosine, produced in response to IR, is generally considered a protective signaling molecule and elicits its physiological responses through four distinct adenosine receptors. The short half-life, lack of specificity and rapid metabolism limits the use of adenosine as a therapeutic agent. Thus, intense research efforts have focused on the synthesis and implementation of specific adenosine receptor agonists and antagonists as potential therapeutic agents for a variety of inflammatory conditions including IR injury.

Areas covered in this review: Current knowledge on IR injury with a focus on lung, heart and kidney and studies that have advanced our understanding of the role of adenosine receptors and the therapeutic potential of adenosine receptor agonists and antagonists for the prevention of IR injury.

What the reader will gain: Insight into the role of adenosine receptor signaling in IR injury.

Take home message: No therapies are currently available that specifically target IR injury; however, targeting of specific adenosine receptors may offer therapeutic strategies in this regard.