Thromboxane A2

Thromboxane A₂

Error creating thumbnail:
Identifiers
CAS Number	57576-52-0 checkY
3D model (JSmol)	Interactive image
ChEBI	CHEBI:15627 ☒N
ChemSpider	4444137 ☒N
ECHA InfoCard
E number
IUPHAR/BPS	4482
KEGG	C02198 ☒N
MeSH	Thromboxane+A2
PubChem CID	5280497
UNII	4C2A5G825S checkY
CompTox Dashboard (EPA)	{{#property:P3117}}
InChI InChI=1S/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18-14-20(24-17)25-18)10-7-4-5-8-11-19(22)23/h4,7,12-13,15-18,20-21H,2-3,5-6,8-11,14H2,1H3,(H,22,23)/b7-4-,13-12+/t15-,16+,17+,18-,20+/m0/s1 ☒N Key: DSNBHJFQCNUKMA-SCKDECHMSA-N ☒N
SMILES CCCCC[C@@H](/C=C/[C@@H]1[C@H]([C@@H]2C[C@@H](O2)O1)C/C=C\CCCC(=O)O)O
Properties
Chemical formula	C20H32O5
Molar mass	352.471 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). ☒N verify (what is checkY☒N ?) Infobox references

Thromboxane A₂ (TXA₂) 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. 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 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 and I-BOP. In human studies, 11-dehydrothromboxane B2 levels are used to indirectly measure TXA₂ production.

File:Eicosanoid synthesis.svg

Eicosanoid synthesis.