The P2 receptors in platelet function.
After vessel wall injury, platelets adhere to the exposed subendothelium, are activated, and release mediators such as thromboxane A (2) (TXA (2)) and nucleotides stored at very high concentration in the so-called dense granules. Among other soluble agents, released nucleotides act in a positive feedback mechanism to cause further platelet activation and amplify platelet responses induced by agents such as thrombin or collagen. Adenine nucleotides act on platelets through three distinct P2 receptors: two are G protein-coupled adenosine diphosphate (ADP) receptors, namely the P2Y (1) and P2Y (12) receptor subtypes; the P2X (1) receptor ligand-gated cation channel is activated by adenosine triphosphate (ATP). The P2Y (1) receptor initiates platelet aggregation but is not sufficient for a full platelet aggregation in response to ADP, whereas the P2Y (12) receptor is responsible for completion of the aggregation to ADP. This receptor, the molecular target of the antithrombotic drug clopidogrel, is responsible for most of the potentiating effects of ADP when platelets are stimulated by agents such as thrombin, collagen, or immune complexes. The P2X (1) receptor is involved in platelet shape change and in activation by collagen under shear conditions. Each of these receptors is coupled to specific signal transduction pathways in response to ADP or ATP and is differentially involved in all of the sequential events involved in platelet function and hemostasis. As such, they represent potential targets for antithrombotic drugs.
Hechler
Béatrice
B
INSERM, Etablissement Français du Sang-Alsace, 10 Rue Spielmann, BP 36-67065 Strasbourg Cedex, France.
Cattaneo
Marco
M
Gachet
Christian
C
D000244:Adenosine Diphosphate / Q000494:pharmacology / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology; D000262:Adenylyl Cyclases / Q000097:blood; D001808:Blood Vessels / Q000293:injuries; D048430:Cell Shape / Q000187:drug effects; D000077144:Clopidogrel; D003594:Cytoplasmic Granules / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology; D008954:Models, Biological; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D020239:Receptor Cross-Talk; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D013927:Thrombosis / Q000188:drug therapy / Q000503:physiopathology; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
D005343:Fibrinolytic Agents; D008565:Membrane Proteins; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000077144:Clopidogrel; D000262:Adenylyl Cyclases; D013988:Ticlopidine