Thromboxane A2 Sample Clauses

Thromboxane A2. Binding of ADP to P2Y12 stimulates phospholipase A2-induced release of arachidonic acid (AA) from phospholipid. AA is converted to prostaglandin (PG) G2 by cyclo-oxygenase-1 (XXX-1), which is then reduced by a peroxidase to PGH2 and subsequently converted to TXA2 via TXA2 synthase 65 66. The thromboxane/PGH2 receptor is present on platelets, as well as monocytes, erythrocytes and endothelial cells. TXA2 binds to the thromboxane/PGH2 receptor, which has two main isoforms: the Gq-coupled TPα, and the Gi-coupled TPβ receptors. These two receptors differ in their C-terminal cytoplasmic domains 70, with the TPα isoform primarily being expressed on platelets 71. TXA2 binding to the TPα receptor leads to activation of both Gs and Gi proteins, with consequent activation of both phospholipase C and adenylyl cyclase, whilst its binding to TPβ results in Gi activation and consequent inhibition of adenylyl cyclase; the net result in platelets being their activation leading to the abovementioned conformational changes and aggregation 72. A series of experiments using transfected cell lines, showed that TXA2 binding to the TPα receptor stimulated adenylyl cyclase and thus increased cAMP formation, whilst opposite effects were seen with the TPβ receptor 73. Aside from platelet activation, TXA2 plays roles in atherogenesis, vascular remodelling, and immunogenicity 74 75, and is a potent vasoconstrictor 76. TXA2 increases the expression of endothelial adhesion molecules, such as ICAM-1 and vascular cell adhesion molecule-1 (VCAM- 1), and plays complex roles in endothelial cell migration 75. Mutations in the TP receptors result in a varied clinical picture, ranging from impaired haemostasis when reduced receptor activity is present to predisposition to thrombosis and infarction 77 78. Due to the short half-life of TXA2, its metabolite, 11-dehydro TXB2 is commonly used when measured in urine as an indirect measure of TXA2 79.