Figure 4.

Ischemia reperfusion injury (I/RI) induces the passive or active release of intracellular ATP to the extracellular space. Once in the extracellular milieu, ATP can activate G-protein-coupled receptors (P2YRs) to stimulate calcium-dependent signaling and the activation of protein kinase C (PKC) allowing the activation of the DUOX complex and the release of H₂O₂. H₂O₂ can cross the cellular membrane via AQP to initiate redox signaling and further promote ATP efflux. Extracellular ATP is metabolized by enzymatic phosphohydrolysis in a two-step process via CD39 conversion of ATP to AMP, and CD73 phosphohydrolysis of AMP to adenosine (Ado). The latter, can mediate anti-inflammatory effects [50,79,84,85].