P2Y12 receptors in platelets and other hematopoietic and non-hematopoietic cells

Abstract

The P2Y₁₂ receptor is a Gi-coupled ADP receptor first described in blood platelets where it plays a central role in the complex processes of activation and aggregation. Platelet granules store important amounts of ADP which are released upon stimulation by interaction of platelets with the damaged vessel wall. Therefore, the P2Y₁₂ receptor is a key player in primary hemostasis and in arterial thrombosis and is an established target of antithrombotic drugs like the thienopyridine compounds ticlopidine, clopidogrel, and prasugrel or the direct, reversible antagonists ticagrelor and cangrelor. Beyond the platelet physiology and pharmacology, recent studies have revealed the expression of the P2Y₁₂ receptor in other hematopoietic cells including leukocyte subtypes and microglia in the central nervous system as well as in vascular smooth muscle cells. These studies indicate putative roles of the P2Y₁₂ receptor in inflammatory states and diseases of the brain, lung, and blood vessels. The selective role of P2Y₁₂ among other P2 receptors as well as the possible impact of P2Y₁₂ targeting drugs in these processes remain to be evaluated.