Thromboxane A2: Difference between revisions

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'''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 [[integrin]]s, and [[degranulation]].<ref>{{Cite journal|last=Offermanns|first=Stefan|date=2006-12-08|title=Activation of Platelet Function Through G Protein–Coupled Receptors|journal=Circulation Research|language=EN|volume=99|issue=12|pages=1293–1304|doi=10.1161/01.res.0000251742.71301.16|pmid=17158345|issn=0009-7330|doi-access=free}}</ref> Circulating [[fibrinogen]] binds these receptors on adjacent platelets, further strengthening the [[clot]]. Thromboxane A2 is also a known [[vasoconstrictor]]<ref>{{Cite journal|last1=Ding|first1=Xueqin|last2=Murray|first2=Paul A.|date=November 2005|title=Cellular mechanisms of thromboxane A2-mediated contraction in pulmonary veins|journal=American Journal of Physiology. Lung Cellular and Molecular Physiology|volume=289|issue=5|pages=L825–833|doi=10.1152/ajplung.00177.2005|issn=1040-0605|pmid=15964897|s2cid=3171857 }}</ref><ref>{{Cite journal|last1=Yamamoto|first1=K.|last2=Ebina|first2=S.|last3=Nakanishi|first3=H.|last4=Nakahata|first4=N.|date=November 1995|title=Thromboxane A2 receptor-mediated signal transduction in rabbit aortic smooth muscle cells|journal=General Pharmacology|volume=26|issue=7|pages=1489–1498|issn=0306-3623|pmid=8690235|doi=10.1016/0306-3623(95)00025-9}}</ref><ref>{{Cite journal|last=Smyth|first=Emer M|date=2010-04-01|title=Thromboxane and the thromboxane receptor in cardiovascular disease|journal=Clinical Lipidology|volume=5|issue=2|pages=209–219|doi=10.2217/CLP.10.11|issn=1758-4299|pmc=2882156|pmid=20543887}}</ref><ref>{{Cite journal|last1=Winn|first1=R|last2=Harlan|first2=J|last3=Nadir|first3=B|last4=Harker|first4=L|last5=Hildebrandt|first5=J|date=September 1983|title=Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.|journal=Journal of Clinical Investigation|volume=72|issue=3|pages=911–918|issn=0021-9738|pmc=1129256|pmid=6886010|doi=10.1172/jci111062}}</ref> 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 receptor|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.

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 thromboxane A2. 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.<ref>{{Cite journal |last1=Francois |first1=Helene |last2=Athirakul |first2=Krairerk |last3=Mao |first3=Lan |last4=Rockman |first4=Howard |last5=Coffman |first5=Thomas M. |date=February 2004 |title=Role for Thromboxane Receptors in Angiotensin-II–Induced Hypertension |journal=Hypertension |language=en |volume=43 |issue=2 |pages=364–369 |doi=10.1161/01.HYP.0000112225.27560.24 |issn=0194-911X|doi-access=free |pmid=14718360 }}</ref>

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]]).<ref>{{cite journal | doi = 10.1093/jb/mvu078 | volume=157 | title=Two distinct leukotriene B4 receptors, BLT1 and BLT2 | year=2014 | journal=Journal of Biochemistry | pages=65–71 | last1 = Yokomizo | first1 = T. | issue=2 | pmid=25480980| doi-access= }}</ref> 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]].<ref>{{cite news|title=Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855 but not Thr-697|author=Michael P. Walsh|display-authors=etal|url=http://biosupport.licor.com/docs/2005/BJ20050237.pdf|url-status=dead|archive-url=https://web.archive.org/web/20110713204304/http://biosupport.licor.com/docs/2005/BJ20050237.pdf|archive-date=2011-07-13}}</ref> In human studies, [[11-dehydrothromboxane B2]] levels are used to indirectly measure TXA2 production.<ref>{{cite journal|title=11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation|vauthors=Catella F, Healy D, Lawson JA, FitzGerald GA|journal=PNAS|year=1986|volume=83|issue=16|pages=5861&ndash;5865|pmid=3461463|doi=10.1073/pnas.83.16.5861|pmc=386396|bibcode=1986PNAS...83.5861C|doi-access=free}}</ref><ref>{{cite journal|vauthors=Lordkipanidzé M, Pharand C, Schampaert E, Turgeon J, Palisaitis DA, Diodati JG|title=A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease|journal=Eur Heart J|year=2007|volume=28|issue=14|pages=1702&ndash;1708|doi=10.1093/eurheartj/ehm226|pmid=17569678|doi-access=free}}</ref>

==References==

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