Nucleotides are emerging as ubiquitous family of extracellular signaling molecules. Their effects are mediated through a specific class of plasma membrane receptors called purinergic P2 receptors that, according to the molecular structure, are further subdivided into two subfamilies: P2Y and P2X. Specifically, P2X receptors (P2XRs) are ligand-gated ion channels, whereas P2Y receptors (P2YRs) belong to the superfamily of G-protein-coupled receptors.