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Chemical Compound Review

thromboxane A2     (Z)-7-[(1S,2R,3S,5S)-3- [(E,3S)-3...

Synonyms: TXA-2, TXA2, SureCN34165, CHEBI:15627, HMDB01452, ...
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Disease relevance of Rabbit aorta contracting substance

  • Thus, (a) treadmill exercise promotes the development of cyclic flow variations in dogs with coronary stenoses and endothelial injury; (b) ventricular pacing does not induce cyclic flow variations in most dogs in the same model; and (c) TXA2 and/or serotonin are important mediators of cyclic flow variations in this model [1].
  • PKC inhibition prevented TXA2-stimulated and Ang II--stimulated VSMC hypertrophy without attenuating the observed increase in bFGF expression [2].
  • In lupus nephritis (LN), renal thromboxane A2 (TXA2) production is increased, and inhibition of TXA2 activity improves renal function [3].
  • Increased tissue TxA2 synthesis may contribute to local thrombosis and decreased graft perfusion during acute rejection, thereby potentiating graft destruction [4].
  • The current study defines the single nephron defect in congenital, unilateral hydronephrosis and evaluates the roles of angiotensin II (Ang II) and TxA2 in this renal derangement [5].

High impact information on Rabbit aorta contracting substance

  • Inositol phosphate accumulation by Gq-coupled M3-muscarinic, thromboxane-A2, and 5-HT2 receptors was desensitized in airway smooth muscle cells from betaAR-/- mice and sensitized in cells from beta2AR-OE mice [6].
  • In contrast to thrombin, the TXA2 mimetic U46619 led to the selective activation of G12 and G13 in Galphaq-deficient platelets indicating that these G proteins mediate TXA2 receptor-induced shape change [7].
  • Platelets lacking the alpha-subunit of the heterotrimeric G protein Gq do not aggregate and degranulate but still undergo shape change after activation through thromboxane-A2 (TXA2) or thrombin receptors [7].
  • Furthermore, evidence is presented that the more unstable and major component of rabbit aorta contracting substance (RCS) formed in platelets and guinea pig lung is also thromboxane A2 [8].
  • Therefore, the focus of this study was to elucidate at least part of the signal transduction network or pathway activated by GPIb-mediated agglutination to cause TxA2 production [9].

Chemical compound and disease context of Rabbit aorta contracting substance


Biological context of Rabbit aorta contracting substance

  • Platelet aggregation, secretion, and thromboxane formation induced by various agonists, including arachidonate, prostaglandin-G2 (PGG2), and thromboxane-A2 (TxA2), were examined in a patient with a bleeding disorder who was previously reported to have a TxA2-related defect [13].
  • ADP, thrombin, or thromboxane A2 (TxA2) signaling through their respective Gq-coupled receptors was normal as assessed by measuring either mobilization of intracellular calcium, diacylglycerol (DAG) generation, or pleckstrin phosphorylation [14].
  • Western analysis confirmed the presence of these isoforms in cultured VSMC lines and demonstrated downregulation of PKC alpha, delta, and epsilon by phorbol 12-myristate 13-acetate (PMA) but not TXA2 or Ang II [2].
  • However, pretreatment with the TxA2 synthesis inhibitor UK-38,485 or with the leukotriene D4/E4 antagonist LY-163,443 markedly blunted the U-46,619-induced increase in renal vascular resistance and the decrease in GFR [15].
  • There are no data so far on whether the excessive TXA2 production in LN derives from upregulation of type I or type II isoforms of COX [3].

Anatomical context of Rabbit aorta contracting substance

  • These results indicate that COX-2 upregulation is a specific finding of active LN and that monocytes infiltrating the glomeruli contribute to the exaggerated local synthesis of TXA2 [3].
  • This implicates enhanced release of TXA2 or its precursor prostanoid, prostaglandin endoperoxide (PGH2), or both, as factors mediating the endothelial cell dysfunction [16].
  • OBJECTIVE: Studies of aortas from hypertensive and diabetic rats and rabbits have demonstrated impairment of endothelium-dependent relaxations, which were associated with increased release of endothelium-derived thromboxane A2 (TXA2) [16].
  • Ca++ mobilization, mostly due to an influx across the plasma membrane, is completely inhibited by aspirin and persists after selective blockade of TxA2 synthase by dazoxiben [17].
  • The effect of human recombinant platelet-derived growth factor (PDGF) isoforms, (r)PDGF-AA, PDGF-AB and PDGF-BB, on contractility of rat aortic rings as well as on intracellular free Ca2+ ([Ca2+]i), intracellular pHi (pHi) and thromboxane A2 (TXA2) formation in cultured vascular smooth muscle cells (VSMC) was examined [18].

Associations of Rabbit aorta contracting substance with other chemical compounds


Gene context of Rabbit aorta contracting substance

  • Thromboxane A2 (TXA2) synthetase inhibitor and TXA2R inhibitor R68070 were able to inhibit platelet aggregation induced by CD69 stimulation, indicating that TXA2 was the main mediator of the response [20].
  • We concluded that anti-PR3 antibodies are potent inducers of monocyte cytokine and prostanoid release, and TNF-alpha, IL-1beta, and TxA2 function as facilitators of the secretory response [24].
  • FMLP produced transient tension changes in human coronary arteries, mainly via the generation of TXA2 and PGI2 [25].
  • Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells [26].
  • The P2Y1 receptor is responsible for ADP-induced shape change and weak and transient aggregation, while the P2Y12 receptor is responsible for the completion and amplification of the response to ADP and to all platelet agonists, including thromboxane A2 (TXA2), thrombin, and collagen [27].

Analytical, diagnostic and therapeutic context of Rabbit aorta contracting substance

  • After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 +/- 31 versus 199 +/- 28 ng iTXB2/ml/5 X 10(5) platelets; P less than 0.05) [19].
  • The thromboxane A2 (TXA2) production in nonseeded grafts was significantly higher than in seeded grafts (p less than 0.001), arterial autografts (p less than 0.001), or in para-anastomotic native artery (p less than 0.001) [28].
  • Histamine levels were measured radioenzymatically; leukotrienes (LTs), prostaglandins (PGs) and thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), were quantitated using an enzyme immunoassay [29].
  • The percentage change in the TXA2 metabolite was positively related to the magnitude of change induced by apheresis in phospholipid bound arachidonic acid [30].
  • Increased [Ca2+]i was associated with increased production of thromboxane A2 (TXA2) as determined by radioimmunoassay of its stable hydrolysis product TXB2, and of 12-hydroxy eicosatetraenoic acid (12-HETE) measured by high performance liquid chromatography [31].


  1. Treadmill exercise promotes cyclic alterations in coronary blood flow in dogs with coronary artery stenoses and endothelial injury. Eidt, J.F., Ashton, J., Golino, P., McNatt, J., Buja, L.M., Willerson, J.T. J. Clin. Invest. (1989) [Pubmed]
  2. Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C. Ali, S., Becker, M.W., Davis, M.G., Dorn, G.W. Circ. Res. (1994) [Pubmed]
  3. Upregulation of renal and systemic cyclooxygenase-2 in patients with active lupus nephritis. Tomasoni, S., Noris, M., Zappella, S., Gotti, E., Casiraghi, F., Bonazzola, S., Benigni, A., Remuzzi, G. J. Am. Soc. Nephrol. (1998) [Pubmed]
  4. Cortical and vascular prostaglandin synthesis during renal allograft rejection in the rat. Gibbons, C.P., Wiley, K.N., Lindsey, N.J., Fox, M., Beck, S., Slater, D.N., Preston, F.E., Brown, C.B., Raftery, A.T. Transplantation (1987) [Pubmed]
  5. Alterations in glomerular dynamics in congenital, unilateral hydronephrosis. Hanss, B.G., Lewy, J.E., Vari, R.C. Kidney Int. (1994) [Pubmed]
  6. Antithetic regulation by beta-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway beta-agonist paradox. McGraw, D.W., Almoosa, K.F., Paul, R.J., Kobilka, B.K., Liggett, S.B. J. Clin. Invest. (2003) [Pubmed]
  7. Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. Klages, B., Brandt, U., Simon, M.I., Schultz, G., Offermanns, S. J. Cell Biol. (1999) [Pubmed]
  8. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Hamberg, M., Svensson, J., Samuelsson, B. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  9. Botrocetin/VWF-induced signaling through GPIb-IX-V produces TxA2 in an alphaIIbbeta3- and aggregation-independent manner. Liu, J., Pestina, T.I., Berndt, M.C., Jackson, C.W., Gartner, T.K. Blood (2005) [Pubmed]
  10. Platelet thromboxane A2/endoperoxide (TXA2/PGH2) receptors in type I diabetes mellitus. Jaschonek, K., Faul, C., Weisenberger, H., Krönert, K., Schröder, H., Renn, W. Thromb. Haemost. (1989) [Pubmed]
  11. Prevention of reocclusion by MCI-9038, a thrombin inhibitor, following t-PA-induced thrombolysis in a canine model of femoral arterial thrombosis. Mellott, M.J., Connolly, T.M., York, S.J., Bush, L.R. Thromb. Haemost. (1990) [Pubmed]
  12. Role of prostaglandins in pregnancy-induced hypertension. Satoh, K., Seki, H., Sakamoto, H. Am. J. Kidney Dis. (1991) [Pubmed]
  13. Impaired platelet response to thromboxane-A2 and defective calcium mobilization in a patient with a bleeding disorder. Lages, B., Malmsten, C., Weiss, H.J., Samuelsson, B. Blood (1981) [Pubmed]
  14. Evidence for a role for Galphai1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Galphai1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder. Patel, Y.M., Patel, K., Rahman, S., Smith, M.P., Spooner, G., Sumathipala, R., Mitchell, M., Flynn, G., Aitken, A., Savidge, G. Blood (2003) [Pubmed]
  15. Renal vasoconstriction with U-46,619; role of arachidonate metabolites. Wilcox, C.S., Folger, W.H., Welch, W.J. J. Am. Soc. Nephrol. (1994) [Pubmed]
  16. Selective impairment of endothelium-dependent relaxations by prostaglandin endoperoxide. Tesfamariam, B. J. Hypertens. (1994) [Pubmed]
  17. Regulation of arachidonic acid-dependent Ca++ influx in human platelets. Bosia, A., Losche, W., Pannocchia, A., Treves, S., Ghigo, D., Till, U., Pescarmona, G. Thromb. Haemost. (1988) [Pubmed]
  18. The platelet-derived growth factor isomers, PDGF-AA, PDGF-AB and PDGF-BB, induce contraction of vascular smooth muscle cells by different intracellular mechanisms. Sachinidis, A., Locher, R., Hoppe, J., Vetter, W. FEBS Lett. (1990) [Pubmed]
  19. Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients. Mayfield, R.K., Halushka, P.V., Wohltmann, H.J., Lopes-Virella, M., Chambers, J.K., Loadholt, C.B., Colwell, J.A. Diabetes (1985) [Pubmed]
  20. Preferential involvement of a phospholipase A2-dependent pathway in CD69-mediated platelet activation. Testi, R., Pulcinelli, F.M., Cifone, M.G., Botti, D., Del Grosso, E., Riondino, S., Frati, L., Gazzaniga, P.P., Santoni, A. J. Immunol. (1992) [Pubmed]
  21. Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study. Axelrod, L., Camuso, J., Williams, E., Kleinman, K., Briones, E., Schoenfeld, D. Diabetes Care (1994) [Pubmed]
  22. Different effects of aspirin, dipyridamole and UD-CG 115 on platelet activation in a model of vascular injury: studies with extracellular matrix covered with endothelial cells. Eldor, A., Vlodavsky, I., Fuks, Z., Muller, T.H., Eisert, W.G. Thromb. Haemost. (1986) [Pubmed]
  23. Biological efficacy of low against medium dose aspirin regimen after coronary surgery: analysis of platelet function. Cornelissen, J., Kirtland, S., Lim, E., Goddard, M., Bellm, S., Sheridan, K., Large, S., Vuylsteke, A. Thromb. Haemost. (2006) [Pubmed]
  24. Wegener's granulomatosis: antiproteinase 3 antibodies induce monocyte cytokine and prostanoid release-role of autocrine cell activation. Hattar, K., Bickenbach, A., Csernok, E., Rosseau, S., Grandel, U., Seeger, W., Grimminger, F., Sibelius, U. J. Leukoc. Biol. (2002) [Pubmed]
  25. FMLP actions and its binding sites in isolated human coronary arteries. Keitoku, M., Kohzuki, M., Katoh, H., Funakoshi, M., Suzuki, S., Takeuchi, M., Karibe, A., Horiguchi, S., Watanabe, J., Satoh, S., Nose, M., Abe, K., Okayama, H., Shirato, K. J. Mol. Cell. Cardiol. (1997) [Pubmed]
  26. Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells. Ishizuka, T., Kawakami, M., Hidaka, T., Matsuki, Y., Takamizawa, M., Suzuki, K., Kurita, A., Nakamura, H. Clin. Exp. Immunol. (1998) [Pubmed]
  27. The platelet P2 receptors as molecular targets for old and new antiplatelet drugs. Gachet, C. Pharmacol. Ther. (2005) [Pubmed]
  28. Prostaglandin production and platelet reactivity of small-diameter grafts. Sicard, G.A., Allen, B.T., Long, J.A., Welch, M.J., Griffin, A., Clark, R.E., Anderson, C.B. J. Vasc. Surg. (1984) [Pubmed]
  29. Contributory role of lung pleura to release of anaphylactic mediators from guinea pig lung in response to ovalbumin or A23187. Wong, W.S., Spaethe, S.M., Henry, D.P., Fleisch, J.H. Biochem. Pharmacol. (1992) [Pubmed]
  30. Arachidonic acid of platelet phospholipids is decreased after extracorporeal removal of plasma low density lipoproteins in patients with familial hypercholesterolemia. Bräutigam, R., Bräutigam, C., Lorenz, R., Richter, W.O., Engelmann, B. Atherosclerosis (1997) [Pubmed]
  31. Effect of cytoplasmic pH on Ca(2+)-stimulated eicosanoid biosynthesis in human platelets. Edwards, J.S., Ritter, J.M. Br. J. Pharmacol. (1994) [Pubmed]
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