Platelet Receptors for Adenine Nucleotides and Thromboxane A₂

 

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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 G_q and phospholipase C, is required for ADP-induced platelet shape change, fibrinogen receptor activation, and TXA₂ generation. The G_i-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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Satya P KunapuliPh.D. 

Department of Physiology, Temple University, Department of Physiology

Rm. 224, OMS, 3420 N. Broad Street

Philadelphia, PA 19140

Email: spk@temple.edu