Figure 1.

Purinergic signaling pathways for purine nucleosides and nucleotides, and pyrimidine nucleotides. Extracellular ATP and other nucleotides originate from intracellular sources through cell damage, cotransmission, pannexin hemichannels, and other mechanisms. These nucleotides act on P2Y (GPCRs, activated by triphosphates, diphosphates and UDP-sugars) and P2X (ion channels, mainly by ATP) receptors. Ectonucleotidases (CD39, CD73) are largely responsible for the formation, from ATP, of adenosine that activates its four receptors. In general, adenosine receptor agonists and P2X/P2Y receptor antagonists induce pain relief in various models.