Thromboxane A<sub>2</sub> (TXA<sub>2</sub>) is a type of thromboxane that is produced by activated platelets during hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by activating the thromboxane receptor, which results in platelet-shape change, inside-out activation of integrins, and degranulation. Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. TXA<sub>2</sub> is also a known vasoconstrictor and is especially important during tissue injury and inflammation. It is also regarded as responsible for Prinzmetal's angina.
Receptors that mediate TXA<sub>2</sub> actions are thromboxane A<sub>2</sub> receptors. The human TXA<sub>2</sub> receptor (TP) is a typical G protein-coupled receptor (GPCR) with seven transmembrane segments. In humans, two TP receptor splice variants â TPñ and TPò â have so far been cloned.
Thromboxane A<sub>2</sub> (TXA<sub>2</sub>) is generated from prostaglandin H<sub>2</sub> by thromboxane-A synthase in a metabolic reaction which generates approximately equal amounts of 12-hydroxyheptadecatrienoic acid (12-HHT). Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H<sub>2</sub>, and therefore TXA<sub>2</sub>. Contrastly, TXA<sub>2</sub> vascular tissue synthesis is stimulated by angiotensin II which promotes cyclooxygenase I's metabolism of arachidonic acid. An angiotensin II dependent pathway also induces hypertension and interacts with TXA<sub>2</sub> receptors.
TXA<sub>2</sub> is very unstable in aqueous solution, since it is hydrated within about 30 seconds to the biologically inactive thromboxane B2. 12-HHT, while once thought to be an inactive byproduct of TXA<sub>2</sub> synthesis, has recently been shown to have a range of potentially important actions, some of which relate to the actions of TXA<sub>2</sub> (see 12-Hydroxyheptadecatrienoic acid). Due to its very short half-life, TXA<sub>2</sub> primarily functions as an autocrine or paracrine mediator in the nearby tissues surrounding its site of production. Most work in the field of TXA<sub>2</sub> is done instead with synthetic analogs such as U46619 and I-BOP. In human studies, 11-dehydrothromboxane B2 levels are used to indirectly measure TXA<sub>2</sub> production.