PathwayStep583 PathwayStep591 PathwayStep576 Signal amplification Authored: Akkerman, JW, 2009-06-03 Edited: Jupe, S, 2009-11-03 In the initial response to injury, platelets adhere to damaged blood vessels, responding to the exposure of collagen from the vascular epithelium. Once adhered they degranulate, releasing stored secondary agents such as ADP and ATP, and synthesized thromboxane A2. These amplify the response, activating and recruiting further platelets to the area and promoting platelet aggregation. Adenosine nucleotides secreted following platelet activation signal through P2 purinergic receptors on the platelet membrane. ADP activates P2Y1 and P2Y12 while ATP activates the ionotropic P2X1 receptor (Kunapuli et al. 2003). Activation of these receptors initiates a complex signaling cascade that ultimately results in platelet activation and thrombus formation (Kahner et al. 2006). ADP stimulation of P2Y1 and P2Y12 involves signaling via both the alpha and gamma:beta components of the heterotrimeric G-protein (Hirsch et al. 2001, 2006). Pubmed11511514 Pubmed12681240 Pubmed16543958 Pubmed17059469 Pubmed18077812 Reactome Database ID Release 43392518 Reactome, http://www.reactome.org ReactomeREACT_20524 Reviewed: Harper, MT, 2009-11-02 Reviewed: Jones, ML, 2009-11-02 Reviewed: Poole, AW, 2009-11-02 ADP signalling through P2Y purinoceptor 12 ADP signalling through P2Y purinoceptor 1 Thromboxane signalling through TP receptor