Thromboxane A₂ (TXA₂) is a type of

thromboxane Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring. Thromboxane is named for ...

that is produced by activated

platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...

during

hemostasis In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...

and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by activating the

thromboxane receptor The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the ''TBXA2R'' gene, The thromboxane receptor is one among the five classes of prostaglandin receptor, prostanoid receptors and was ...

, which results in platelet-shape change, inside-out activation of

integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...

s, and degranulation. Circulating

fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

binds these receptors on adjacent platelets, further strengthening the

clot A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...

. TXA₂ 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 TXA₂ actions are thromboxane A₂ receptors. The human TXA₂ receptor (TP) is a typical G protein-coupled receptor (GPCR) with seven transmembrane segments. In humans, two TP receptor splice variants – TPα and TPβ – have so far been cloned.

Synthesis and breakdown

Thromboxane A₂ (TXA₂) is generated from prostaglandin H₂ by thromboxane-A synthase in a metabolic reaction which generates approximately equal amounts of 12-hydroxyheptadecatrienoic acid (12-HHT).

Aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H₂, and therefore TXA₂. Contrastly, TXA₂ 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 TXA₂ receptors. TXA₂ 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 TXA₂ synthesis, has recently been shown to have a range of potentially important actions, some of which relate to the actions of TXA₂ (see 12-Hydroxyheptadecatrienoic acid). Due to its very short half life, TXA₂ primarily functions as an autocrine or paracrine mediator in the nearby tissues surrounding its site of production. Most work in the field of TXA₂ is done instead with synthetic analogs such as

U46619 U46619 is a stable synthetic Structural analog, analog of the endoperoxide prostaglandin PGH2 first prepared in 1975, and acts as a thromboxane A2 (TP) receptor agonist. It potently stimulates TP receptor-mediated, but not other prostaglandin rec ...

and I-BOP. In human studies, 11-dehydrothromboxane B2 levels are used to indirectly measure TXA₂ production.

References

{{Prostanoidergics Eicosanoids