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...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2006-11, Vol.4 (11), p.2317-2326
Main Authors: KAHNER, B. N., SHANKAR, H., MURUGAPPAN, S., PRASAD, G. L., KUNAPULI, S. P.
Format: Article
Language:English
Subjects:
Adenine Nucleotides - metabolism
Animals
Blood Platelets - metabolism
Blood Vessels - injuries
Blood Vessels - metabolism
Collagen - metabolism
Cytoplasmic Granules - secretion
GPCR
Humans
P2X1
P2Y1
P2Y12
Platelet Aggregation
Purinergic Agonists
Receptors, Purinergic - metabolism
Signal Transduction
Thrombin - metabolism
Thromboxane A2 - metabolism
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Summary: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.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2006.02192.x