Nucleotide receptor signaling in platelets.
Upon injury to a vessel wall the exposure of subendothelial collagen results in the activation of platelets. Platelet activation culminates in shape change, aggregation, release of granule contents and generation of lipid mediators. These secreted and generated mediators trigger a positive feedback mechanism potentiating the platelet activation induced by physiological agonists such as collagen and thrombin. Adenine nucleotides, adenosine diphosphate (ADP) and adenosine triphosphate (ATP), released from damaged cells and that are secreted from platelet-dense granules, contribute to the positive feedback mechanism by acting through nucleotide receptors on the platelet surface. ADP acts through two G protein-coupled receptors, the Gq-coupled P2Y1 receptor, and the Gi-coupled P2Y12 receptor. ATP, on the other hand, acts through the ligand-gated channel P2X1. Stimulation of platelets by ADP leads to shape change, aggregation and thromboxane A2 generation. ADP-induced dense granule release depends on generated thromboxane A2. Furthermore, costimulation of both P2Y1 and P2Y12 receptors is required for ADP-induced platelet aggregation. ATP stimulation of P2X1 is involved in platelet shape change and helps to amplify platelet responses mediated by agonists such as collagen. Activation of each of these nucleotide receptors results in unique signal transduction pathways that are important in the regulation of thrombosis and hemostasis.
Kahner
B N
BN
The Cell Signaling Group, Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA.
Shankar
H
H
Murugappan
S
S
Prasad
G L
GL
Kunapuli
S P
SP
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001808:Blood Vessels / Q000293:injuries / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation; D058913:Purinergic Agonists; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism
D000227:Adenine Nucleotides; D058913:Purinergic Agonists; D011983:Receptors, Purinergic; D013928:Thromboxane A2; D003094:Collagen; D013917:Thrombin