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{{DISPLAYTITLE:Thromboxane A<sub>2</sub>}} |
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| Name = Thromboxane A<sub>2</sub> |
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| verifiedrevid = 411950909 |
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| verifiedrevid = 439079919 |
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| ImageFile = Thromboxane A2 acsv.svg |
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| ImageFile = Thromboxane A2 acsv.svg |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| IUPHAR_ligand = 4482 |
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| CASNo = 57576-52-0 |
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| CASNo_Ref = {{cascite|correct|??}} |
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| PubChem = 5280497 |
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| SMILES = |
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| CASNo = 57576-52-0 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| MeSHName = Thromboxane+A2 |
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| UNII = 4C2A5G825S |
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| PubChem = 5280497 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 4444137 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 15627 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = C02198 |
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| MeSHName = Thromboxane+A2 |
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| SMILES = CCCCC(/C=C/1(2C(O2)O1)C/C=C\CCCC(=O)O)O |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 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 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = DSNBHJFQCNUKMA-SCKDECHMSA-N |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=20 | H=32 | O=5 |
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| Formula = {{Carbon|20}}{{Hydrogen|32}}{{Oxygen|5}} |
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| Appearance = |
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| MolarMass = 352.465 g/mol |
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| Section3 = {{Chembox Hazards |
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'''Thromboxane A<sub>2</sub>''' ('''TXA<sub>2</sub>''') is a type of ] that is produced by activated ] during ] and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by activating the ], which results in platelet-shape change, inside-out activation of ]s, and ].<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 ] binds these receptors on adjacent platelets, further strengthening the ]. TXA<sub>2</sub> is also a known ]<ref>{{Cite journal|last1=Ding|first1=Xueqin|last2=Murray|first2=Paul A.|date=November 2005|title=Cellular mechanisms of thromboxane A<sub>2</sub>-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 A<sub>2</sub> 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 A<sub>2</sub> 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 ]. |
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'''Thromboxane A2''' (TXA2) is a ]. It is produced by activated platelets and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating ] binds these receptors on adjacent platelets, further strengthening the clot. |
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Receptors that mediate TXA2 actions are ]. 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. |
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Receptors that mediate TXA<sub>2</sub> actions are ]. 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 – TPα and TPβ – have so far been cloned. |
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==Synthesis and breakdown== |
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==Synthesis and breakdown== |
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Thromboxane A<sub>2</sub> (TXA<sub>2</sub>) is generated from ] by ] in a metabolic reaction which generates approximately equal amounts of ] (12-HHT). ] irreversibly inhibits platelet ] 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.<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> |
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TXA2 is generated from ] by ]. ] irreversibly inhibits platelet ] preventing the formation of prostaglandin H2, and therefore thromboxane A2. |
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TXA2 is very unstable in aqueous solution, since it is hydrolyzed within about 30 seconds to the biologically inactive ]. 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 ] and ].<ref>{{cite article|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, et all|url=http://biosupport.licor.com/docs/2005/BJ20050237.pdf}} </ref> In human studies, ] 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|author=Catella F, Healy D, Lawson JA, FitzGerald GA|journal=PNAS|year=1986|volume=83|issue=16|pages=5861–5865|url=http://www.pnas.org/content/83/16/5861.abstract|pmid=3461463|doi=10.1073/pnas.83.16.5861|pmc=386396}}</ref><ref>{{cite journal|author=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=1702–1708|doi=10.1093/eurheartj/ehm226|pmid=17569678}}</ref> |
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TXA<sub>2</sub> is very unstable in aqueous solution, since it is hydrated within about 30 seconds to the biologically inactive ]. 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 ]).<ref>{{cite journal | doi = 10.1093/jb/mvu078 | volume=157 | title=Two distinct leukotriene B<sub>4</sub> 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, 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 ] and ].<ref name= Wilson >{{cite journal |vauthors=Wilson DP, Susnjar M, Kiss E, Sutherland C, Walsh MP |date=April 2005 |title=Thromboxane A<sub>2</sub>-induced contraction of rat caudal arterial smooth muscle involves activation of Ca<sup>2+</sup> entry and Ca<sup>2+</sup> sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697 |journal=Biochemical Journal |volume=389(Pt 3) |pages=763-774 |publisher= Portland Press |doi=10.1042/BJ20050237 |pmc=1180727 |pmid=15823093 }}</ref> In human studies, ] levels are used to indirectly measure TXA<sub>2</sub> production.<ref>{{cite journal|title=11-Dehydrothromboxane B<sub>2</sub>: a quantitative index of thromboxane A<sub>2</sub> formation in the human circulation|vauthors=Catella F, Healy D, Lawson JA, FitzGerald GA|journal=PNAS|year=1986|volume=83|issue=16|pages=5861–5865|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=1702–1708|doi=10.1093/eurheartj/ehm226|pmid=17569678|doi-access=free}}</ref> |
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==References== |
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{{Reflist|30em}} |
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{{Eicosanoids}} |
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{{Eicosanoids}} |
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{{Prostanoidergics}} |
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== References == |
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{{reflist}} |
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{{biochem-stub}} |
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