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. The P2Y receptors are differentially expressed in several tissue types, such as heart, lung and brain. However, all P2Y receptors are expressed in leukocytes, which suggests a role for the P2Y receptor family in the activation of leukocytes and platelets in response to inflammation or vascular damage.