Nucleotides are emerging as important extracellular signaling molecules that mediate several effects, such as proliferation, differentiation , chemotaxis and cytokine release. The P2 receptor family is activated by the binding of nucleotides and is divided into two subfamilies, P2X and P2Y. The P2X receptor family is comprised of ligand-gated ion channels that allow for the increased permeability of calcium into the cell in response to extracellular ATP. The P2Y receptor family are G protein-coupled receptors which mediate the effects of extracellular nucleotides, primarily through the activation of phospholipase C. To some extent, the P2Y receptors can also activate potassium channels or, alternatively, inhibit adenylate cyclase and N-type calcium channels in response to extracellular nucleotides. Human platelets express two G protein-coupled nucleotide receptors, P2Y1 and P2Y12. P2Y12 is a receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. P2Y12 is an integral membrane protein involved in platelet aggregation. It is highly expressed in platelets, with lower levels in the brain, lung, appendix, pituitary and adrenal gland.