Platelet Receptors for Adenine Nucleotides and Thromboxane A2

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Abstract
Adenosine diphosphate (ADP) and thromboxane A2 (TXA2) are important physiological activators of platelets and exert their effects by acting on cell surface receptors. Platelet nucleotide receptors can be distinguished as three separate subtypes of the P2 receptor family. The P2X1 receptor is a ligand-gated adenosine triphosphate (ATP) receptor that was originally mistaken for an ADP receptor. This calcium-influx-causing receptor mediates platelet shape change and plays an important role in thrombus formation in small arterioles. The P2Y1 receptor, through activation of Gq and phospholipase C, is required for ADP-induced platelet shape change, fibrinogen receptor activation, and TXA2 generation. The Gi-coupled P2Y12 receptor plays an important role in platelet aggregation, potentiation of dense granule release, and TXA2 generation. Both the P2Y receptors are crucial for in vivo thrombus formation. TXA2 stimulates two subtypes of G protein-coupled TP receptor, TPα and TPβ, but its effects in platelets are mediated predominantly through the α isoform. Although interference with the activation of G protein-coupled ADP or TP receptors results in increased bleeding times and protection from thromboembolism, TP receptor antagonists did not translate into effective antiplatelet drugs. Blockade of ADP receptor is a mode of newer classes of antithrombotic drugs in the coming era. This review focuses on the contribution of different nucleotide receptors and TP receptors to platelet function and their potential as antithrombotic agents.

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