PathwayStep525 PathwayStep534 PathwayStep535 PathwayStep546 PathwayStep555 Binding of ATP to P2X1 Platelet sensitization by LDL Platelet calcium homeostasis Nitric oxide stimulates guanylate cyclase Platelet homeostasis Authored: Akkerman, JW, 2009-06-03 Edited: Jupe, S, 2010-06-07 Pubmed10798271 Pubmed16297879 Reactome Database ID Release 43418346 Reactome, http://www.reactome.org ReactomeREACT_23876 Reviewed: Kunapuli, SP, 2010-06-07 Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in character. Under acute vascular trauma, vasoconstrictor mechanisms predominate and the endothelium becomes prothrombotic, procoagulatory and proinflammatory in nature. This is achieved by a reduction of endothelial dilating agents: adenosine, NO and prostacyclin; and by the direct action of ADP, serotonin and thromboxane on vascular smooth muscle cells to elicit their contraction (Becker et al. 2000). Cyclooxygenase-2 (COX-2) and endothelial nitric oxide synthase (eNOS) are primarily expressed in endothelial cells. Both are important regulators of vascular function. Under normal conditions, laminar flow induces vascular endothelial COX-2 expression and synthesis of Prostacyclin (PGI2) which in turn stimulates endothelial Nitric Oxide Synthase (eNOS) activity. PGI2 and NO both oppose platelet activation and aggregation, as does the CD39 ecto-ADPase, which decreases platelet activation and recruitment by metabolizing platelet-released ADP. Prostacyclin signalling through prostacyclin receptor