The family of purinergic receptors: classification, structure, and signaling pathway. The family of purinergic receptors comprises 2 major groups of membrane receptors: adenosine-activated P1 receptors (P1Rs) and nucleotide-activated P2 receptors (P2Rs). Based on pharmacologic profile and molecular structure, 2 subfamilies have been identified within P2Rs, namely, P2XRs and P2YRs. P2XRs (composing 7 subtypes, P2X1R through P2X7R) are trimeric ATP-gated plasma membrane channels, whereas P2YRs are classic G protein-coupled receptors. Based on their ligand selectivity, P2YRs are further subdivided in subtypes preferentially responding to ATP (human and rodent P2Y1R, and human P2Y11R), to ADP (P2Y12R and P2Y13R), uridine-5′-phosphate (UTP) and UDP (human P2Y4R and P2Y6R), and ATP and UTP (human and rodent P2Y2R and rodent P2Y4R), whereas human P2Y14R binds sugar-linked nucleotides, such as UDP-glucose and UDP-galactose. Two different signaling cascades are associated with P2YRs: some subtypes mainly couple to Gq proteins (P2Y1R, P2Y2R, P2Y4R, P2Y6R, and P2Y11R), whereas others preferentially couple to Gi proteins (P2Y11R, P2Y12R, P2Y13R, and P2Y14R), with P2Y11R activating both molecular pathways.