Purinergic signaling circuitry. The inflammatory response to infection or tissue damage depends on the coordination of adenine nucleotide metabolism and signaling among many cell types via purinergic receptors that recognize ATP, ADP, or adenosine. A neutrophil migrating toward a chemotactic stimulus (fMLP) releases ATP from its leading edge. ATP is dephosphorylated by ectoenzymes (CD39 and CD73) to ADP and adenosine. Gradients of ATP and adenosine initiate and accelerate directional chemotaxis via P2Y2 and A3 adenosine receptors, respectively, on neutrophils. Other adenosine receptors (A2A and A2B) inhibit neutrophil chemotaxis and adhesion to endothelial cells, as well as platelet aggregation.