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 its ...

that is produced by activated

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

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. This involves coagulation, whi ...

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 prostanoid receptors and was the first eicosanoid re ...

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

integrins Integrins are transmembrane receptors that facilitate 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, ...

, and degranulation. Circulating

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

binds these receptors on adjacent platelets, further strengthening the

clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...

. Thromboxane A2 is also a known

vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...

and is especially important during tissue injury and inflammation. It is also regarded as responsible for

Prinzmetal's angina Variant angina, also known as Prinzmetal angina, vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina (cardiac chest pain). Variant angina differs from stable 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

TXA2 is generated from

prostaglandin H2 Prostaglandin H2 is a type of prostaglandin and a precursor for many other biologically significant molecules. It is synthesized from arachidonic acid in a reaction catalyzed by a cyclooxygenase enzyme. The conversion from Arachidonic acid to Pro ...

thromboxane-A synthase Thromboxane A synthase 1 (, platelet, cytochrome P450, family 5, subfamily A), also known as TBXAS1, is a cytochrome P450 enzyme that, in humans, is encoded by the ''TBXAS1'' gene. Function This gene encodes a member of the cytochrome P450 supe ...

in a metabolic reaction which generates approximately equal amounts of 12-Hydroxyheptadecatrienoic acid (12-HHT).

Aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

irreversibly inhibits platelet

cyclooxygenase 1 Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prosta ...

preventing the formation of prostaglandin H2, and therefore thromboxane A2. TXA2 is very unstable in aqueous solution, since it is hydrated within about 30 seconds to the biologically inactive

thromboxane B2 Thromboxane B2 is an inactive metabolite/product of thromboxane A2. It is almost completely cleared in the urine. It itself is not involved in platelet activation and aggregation in case of a wound, but its precursor, thromboxane A2, is. Thrombox ...

. 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 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 receptor-mediated res ...

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

References

{{Prostanoidergics Eicosanoids