Adenosine, an endogenous distress signal, modulates tissue damage and repair

Adenosine is formed inside cells or on their surface, mostly by breakdown of adenine nucleotides. The formation of adenosine increases in different conditions of stress and distress. Adenosine acts on four G-protein coupled receptors: two of them, A1 and A3, are primarily coupled to Gi family G proteins; and two of them, A2A and A2B, are mostly coupled to Gs like G proteins. These receptors are antagonized by xanthines including caffeine. Via these receptors it affects many cells and organs, usually having a cytoprotective function. Joel Linden1 recently grouped these protective effects into four general modes of action: increased oxygen supply/demand ratio, preconditioning, anti-inflammatory effects and stimulation of angiogenesis. This review will briefly summarize what is known and what is not in this regard. It is argued that drugs targeting adenosine receptors might be useful adjuncts in many therapeutic approaches.