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P2Y Purinoceptor Family

P2Y receptors are a class of G-protein-coupled receptors for extracellular nucleotides expressed in almost all human cells. P2Y receptors are widely expressed and play important roles in physiology and pathophysiology. The ADP-induced platelet aggregation is mediated by P2Y1 and P2Y12 receptors, which are used for the prevention and therapy of cardiovascular events. In addition, P2Y receptors are crucial to the nervous system. Adenine nucleotides regulate neuronal activity and neuronal fibre outgrowth by activating the P2Y1 receptors and control migration of microglia by the P2Y12 receptors. UDP stimulates microglial phagocytosis by activating the P2Y6 receptors. Interestingly, recent findings reveal a prominent role for P2Y2 receptors in Alzheimer's disease pathology. The P2Y receptor subtypes are highly diverse in their amino acid sequences and their pharmacological profiles. Selective receptor ligands have been developed for the pharmacological characterization of the receptor subtypes. The study of three-dimensional crystal structures of the P2Y1 and P2Y12 receptors will facilitate the development of therapeutic agents that selectively target P2Y receptors.

Simplified illustration of extracellular purinergic signaling. Fig.1 Simplified illustration of extracellular purinergic signaling.

Based on pharmacology, signal transduction, and structural similarity, P2Y receptors are divided into two subfamilies. Receptors of the first subfamily (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11) are coupled via the Gq-proteins to stimulate phospholipase C followed by increases in inositol phosphates and mobilization of Ca2+ from intracellular stores. In contrast, the P2Y12 receptor subfamily (P2Y12, P2Y13, and P2Y14) signals primarily by activating the Gi proteins and inhibiting the adenylate cyclase activity or controlling the ion channel activity. The non-consecutive numbering of the mammalian P2Y receptors is due to the assignment of the P2Y nomenclature to species homologs or to proteins that has not been demonstrated as an extracellular nucleotide receptor function.

Human P2Y Purinoceptor Members
P2RY1 P2RY10 P2RY11 P2RY12 P2RY13
P2RY14 P2RY2 P2RY4 P2RY6 P2RY8

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