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Chemical Compound Review

AC1L18QD     7-[3-(3-hydroxyoct-1-enyl)- 4,7...

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Disease relevance of thromboxane A2


High impact information on thromboxane A2

  • Isolated glomeruli from nephrotic rats studied 14 or 30 d after a single intravenous injection of adriamycin (7.5 mg/kg) when animals were heavily proteinuric generated significantly more TxB2, the stable breakdown product of TxA2, than normal glomeruli [6].
  • Thromboxane synthase inhibitors suppress TXA2 formation and increase the synthesis of the antiaggregatory prostaglandins PGI2 and PGD2; however, accumulated PGH2 may interact with the platelet and vessel wall TXA2 receptor, thus reducing the antiplatelet effects of this class of drug [1].
  • All of these compounds are inhibitors of platelet aggregation induced by TXA2 or by its stable mimetic, U-46619 [7].
  • Possible alternative or additional reasons for the general lack of success with TXSIs could be that some of the diseases studied do not involve TXA2 or that accumulating prostaglandin endoperoxides in the presence of thromboxane synthase inhibition substitute for TXA2 in causing platelet aggregation [7].
  • BM 13.177 has also proven effective in preventing restenosis after angioplasty, occlusion of coronary artery bypass grafts, and the deleterious effects of TXA2 in renal disease [7].

Chemical compound and disease context of thromboxane A2

  • To investigate the role of thromboxane A2 (TxA2) in murine lupus, we assessed the effects of the specific thromboxane receptor antagonist GR32191 on immune complex glomerulonephritis in MRL-lpr/lpr mice [8].
  • In ischemia-reperfusion IPL, infusion of SQ 29548 (10(-6) M), a specific TxA2/prostaglandin H2 receptor antagonist, attenuated the PA pressor response and the degree of edema [9].
  • Employing a thromboxane A2 (TXA2) receptor antagonist (BAY U 3405) in the presence of LD100 Escherichia coli challenge, we blocked the acute pulmonary hypertensive phase and prevented early mortality, however, TXA2 blockade did not affect the latter development of septic shock and death [10].
  • The macrophage products, leukotriene B4 (LTB4), thromboxane A2 (TXA2), and procoagulant activity (PCA), initiate inflammatory cascades that lead to microvascular thrombosis and neutrophil infiltration, two common features of ARDS [11].
  • The increase in brain endogenous TXA2 levels involves a decrease in blood pressure evoked by haemorrhage because the blockade of TXA2 synthesis by furegrelate pretreatment attenuated the haemorrhagic hypotension [12].

Biological context of thromboxane A2


Anatomical context of thromboxane A2

  • Thromboxane A2 (TXA2) has been implicated in the pathogenesis of progressive glomerulosclerosis and stimulates the synthesis of matrix protein by mesangial cells (MCs) [16].
  • CONCLUSION: These data suggested that the contraction elicited by 2-AG resulted from the vascular smooth muscle cell uptake and conversion of 2-AG to constrictor prostanoid TXA2, which in turn caused vasoconstriction through the stimulation of TP receptor [17].
  • These experiments provide evidence that TXA2 is capable of promoting contractions in the pregnant rat uterus and may be important in the labor mechanism [18].
  • We have studied the effect of amniotic fluid on thromboxane A2 (TXA2) production as an initial step in an evaluation of the role of this metabolite as the mediator of the pulmonary hypertension that accompanies perinatal aspiration [19].
  • Following perinatal aspiration, in situ production of thrombin and proaggregatory TXA2 could recruit more platelets, enhance local TXA2 production, and be responsible for the platelet thrombi that have been documented at autopsy in the pulmonary microcirculation in infants with perinatal aspiration syndrome [19].

Associations of thromboxane A2 with other chemical compounds

  • The activation of TXA2 or P2Y12 receptors alone, which in Galpha(q)-deficient platelets couple to G12/G13 and Gi, respectively, did not induce platelet integrin activation or aggregation [20].
  • The TXA2 receptor antagonist, SQ29548, PGE1, and the ADP scavenger, apyrase, differentially inhibit the aggregation response and TXA2 synthesis in response to Ppep [21].
  • Reperfusion of ischemic brain is associated with production of thromboxane A2 (TXA2), a proaggregatory vasoconstrictor [22].
  • At 2 or 5 h after the end of resuscitation, the liver was isolated and perfused and portal inflow pressure, bile flow, and release of ET-1 and thromboxane B2 (TXB2; a stable metabolite of TXA2) into the perfusate were measured [23].
  • Delaying transfer of media until 10 min after addition of AA did not elicit either aggregation or contractile response, consistent with the short production interval and half-life of TXA2 [18].

Gene context of thromboxane A2

  • The potent effect of TxA2 on platelet function and vascular activity suggests a possible involvement of TS in normal and pathophysiological conditions such as cardiovascular disease [24].
  • 6. We concluded that TXA2 can induce direct contraction of human isolated urinary bladder through the classical TXA2 receptor [25].
  • Moreover, we suggest the presence of prejunctional TXA2 and FP receptors, potentiating acetylcholine release from cholinergic nerve terminals [25].
  • Thromboxane synthase (TS) is a cytochrome P-450 (CYP450) enzyme catalyzing the conversion of prostaglandin endoperoxide (PGH2) into thromboxane A2 (TxA2) which plays a crucial role in hemostasis and cardiovascular diseases [26].
  • Therefore, the aim of these studies was to compare the antihypertensive efficacy of an ANG II type I (AT1) and a TxA2/PGH2 receptor antagonist during different phases of 2K,1C hypertension [27].

Analytical, diagnostic and therapeutic context of thromboxane A2

  • The mean +/- SEM brain level of TXB2, the stable metabolite of TXA2, determined after 60 minutes of reperfusion was 101 +/- 20 pg/mg brain protein in five ischemic control rats [22].
  • To explore biochemical alterations of partially depleted platelets, we studied platelet thromboxane A2 (TXA2) synthesis in citrated platelet-rich plasma (PRP) upon stimulation with thrombin or collagen in 45 recipients of renal allografts and 10 healthy volunteers [28].
  • Production of TXA2 by minced lung tissue was determined by radioimmunoassay of its stable metabolite TXB2 [29].
  • Thirty minutes after ligation of the left anterior descending coronary artery (LAD) in anesthetized cats, the TxA2 receptor antagonist BM-13,177 or its vehicle was given as a bolus injection at 20 mg/kg, followed by continuous infusion of 20 mg/kg/hr for 4.5 hours [30].
  • BACKGROUND: The purpose of this study was to determine the role of thromboxane A2 (TXA2) in a conscious, chronically instrumented rat model of pregnancy-induced hypertension (PIH) produced by chronic reductions in uterine perfusion pressure (RUPP) [31].


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  2. Effect of thromboxane and serotonin receptor antagonists on intracoronary platelet deposition in dogs with experimentally stenosed coronary arteries. Golino, P., Buja, L.M., Ashton, J.H., Kulkarni, P., Taylor, A., Willerson, J.T. Circulation (1988) [Pubmed]
  3. Thromboxane is produced in response to intracoronary infusions of complement C5a in pigs. Cyclooxygenase blockade does not reduce the myocardial ischemia and leukocyte accumulation. Ito, B.R., Roth, D.M., Chenoweth, D.E., Lefer, A.M., Engler, R.L. Circ. Res. (1989) [Pubmed]
  4. Internalization of the TXA2 receptor alpha and beta isoforms. Role of the differentially spliced cooh terminus in agonist-promoted receptor internalization. Parent, J.L., Labrecque, P., Orsini, M.J., Benovic, J.L. J. Biol. Chem. (1999) [Pubmed]
  5. Arthur C. Corcoran Memorial Lecture. The role of eicosanoids in angiotensin-dependent hypertension. Nasjletti, A. Hypertension (1998) [Pubmed]
  6. Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis. Remuzzi, G., Imberti, L., Rossini, M., Morelli, C., Carminati, C., Cattaneo, G.M., Bertani, T. J. Clin. Invest. (1985) [Pubmed]
  7. Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review. Fiddler, G.I., Lumley, P. Circulation (1990) [Pubmed]
  8. Thromboxane receptor blockade reduces renal injury in murine lupus nephritis. Spurney, R.F., Fan, P.Y., Ruiz, P., Sanfilippo, F., Pisetsky, D.S., Coffman, T.M. Kidney Int. (1992) [Pubmed]
  9. Thromboxane contributes to pulmonary hypertension in ischemia-reperfusion lung injury. Zamora, C.A., Baron, D.A., Heffner, J.E. J. Appl. Physiol. (1993) [Pubmed]
  10. Thromboxane-blocked swine as an experimental model of severe intravascular inflammation and septic shock. Jesmok, G., Gundel, R. Shock (1995) [Pubmed]
  11. Ketoconazole inhibits alveolar macrophage production of inflammatory mediators involved in acute lung injury (adult respiratory distress syndrome). Williams, J.G., Maier, R.V. Surgery (1992) [Pubmed]
  12. Involvement of brain thromboxane A in hypotension induced by haemorrhage in rats. Yalcin, M., Cavun, S., Yilmaz, M.S., Cengiz, F., Savci, V. Clin. Exp. Pharmacol. Physiol. (2005) [Pubmed]
  13. Expression, purification, and spectroscopic characterization of human thromboxane synthase. Hsu, P.Y., Tsai, A.L., Kulmacz, R.J., Wang, L.H. J. Biol. Chem. (1999) [Pubmed]
  14. Inhibition of thromboxane A synthesis in U937 cells by glucocorticoids. Lack of evidence for lipocortin 1 as the second messenger. Bienkowski, M.J., Petro, M.A., Robinson, L.J. J. Biol. Chem. (1989) [Pubmed]
  15. Rapid, agonist-dependent phosphorylation in vivo of human thromboxane receptor isoforms. Minimal involvement of protein kinase C. Habib, A., Vezza, R., Créminon, C., Maclouf, J., FitzGerald, G.A. J. Biol. Chem. (1997) [Pubmed]
  16. Role for transforming growth factor beta in thromboxane-induced increases in mesangial cell fibronectin synthesis. Negrete, H., Studer, R.K., Craven, P.A., DeRubertis, F.R. Diabetes (1995) [Pubmed]
  17. 2-Arachidonoyl glycerol induces contraction of isolated rat aorta: role of cyclooxygenase-derived products. Stanke-Labesque, F., Mallaret, M., Lefebvre, B., Hardy, G., Caron, F., Bessard, G. Cardiovasc. Res. (2004) [Pubmed]
  18. Effect of platelet-generated thromboxane on contractions of the pregnant rat uterus. Dubin, N.H., Blake, D.A., Egner, P.G., Ghodgaonkar, R.B. Biol. Reprod. (1982) [Pubmed]
  19. Effect of amniotic fluid on platelet thromboxane production. Stuart, M., Wu, J., Sunderji, S., Ganley, C. J. Pediatr. (1987) [Pubmed]
  20. Costimulation of Gi- and G12/G13-mediated signaling pathways induces integrin alpha IIbbeta 3 activation in platelets. Nieswandt, B., Schulte, V., Zywietz, A., Gratacap, M.P., Offermanns, S. J. Biol. Chem. (2002) [Pubmed]
  21. A sequence within the cytoplasmic tail of GpIIb independently activates platelet aggregation and thromboxane synthesis. Stephens, G., O'Luanaigh, N., Reilly, D., Harriott, P., Walker, B., Fitzgerald, D., Moran, N. J. Biol. Chem. (1998) [Pubmed]
  22. Effect of thromboxane synthase inhibition on eicosanoid levels and blood flow in ischemic rat brain. Pettigrew, L.C., Grotta, J.C., Rhoades, H.M., Wu, K.K. Stroke (1989) [Pubmed]
  23. Role of thromboxane in producing portal hypertension following trauma-hemorrhage. Yokoyama, Y., Toth, B., Kitchens, W.C., Schwacha, M.G., Bland, K.I., Chaudry, I.H. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  24. Mapping of the human thromboxane synthase gene (TBXAS1) to chromosome 7q34-q35 by two-color fluorescence in situ hybridization. Chase, M.B., Baek, S.J., Purtell, D.C., Schwartz, S., Shen, R.F. Genomics (1993) [Pubmed]
  25. Pharmacological characterization of thromboxane and prostanoid receptors in human isolated urinary bladder. Palea, S., Toson, G., Pietra, C., Trist, D.G., Artibani, W., Romano, O., Corsi, M. Br. J. Pharmacol. (1998) [Pubmed]
  26. Genomic structure and polymorphism of the human thromboxane synthase-encoding gene. Baek, S.J., Lee, K.D., Shen, R.F. Gene (1996) [Pubmed]
  27. AT1 and TxA2/PGH2 receptors maintain hypertension throughout 2K,1C Goldblatt hypertension in the rat. Wilcox, C.S., Cardozo, J., Welch, W.J. Am. J. Physiol. (1996) [Pubmed]
  28. In vitro thromboxane synthesis of depleted blood platelets following renal transplantation. Scharf, R.E. Thromb. Haemost. (1990) [Pubmed]
  29. Annexin I concentration, phospholipase activity and thromboxane synthesis in irradiated rat lung. Ts'ao, C., Tsao, F.H., Taylor, J.M., Ward, W.F., Molteni, A. Radiat. Res. (1995) [Pubmed]
  30. Anti-ischemic actions of a new thromboxane receptor antagonist during acute myocardial ischemia in cats. Brezinski, M.E., Yanagisawa, A., Darius, H., Lefer, A.M. Am. Heart J. (1985) [Pubmed]
  31. Enhanced thromboxane synthesis during chronic reductions in uterine perfusion pressure in pregnant rats. Llinás, M.T., Alexander, B.T., Seedek, M., Abram, S.R., Crell, A., Granger, J.P. Am. J. Hypertens. (2002) [Pubmed]
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