thromboxane a synthase

Summary

Summary: An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC 5.3.99.5.

Top Publications

  1. Yokoyama C, Miyata A, Ihara H, Ullrich V, Tanabe T. Molecular cloning of human platelet thromboxane A synthase. Biochem Biophys Res Commun. 1991;178:1479-84 pubmed
    Complementary DNA coding for thromboxane A synthase was amplified by polymerase chain reaction using primers synthesized according to the partial amino acid sequences of human platelet thromboxane A synthase (Nüsing, R...
  2. Fujimura M, Ogawa H, Saito M, Sakamoto S, Miyake Y, Matsuda T. Inhibitory effect of inhalation of a thromboxane synthetase inhibitor on bronchoconstriction induced by aerosolized leukotriene C4 and thromboxane A2 analogue in anesthetized guinea pigs. Allergy. 1991;46:534-9 pubmed
  3. Hoshino M, Fukushima Y. Effect of OKY-046 (thromboxane A2 synthetase inhibitor) on exercise-induced asthma. J Asthma. 1991;28:19-29 pubmed
    ..In other words, the fact that TxA2 was a mediator of EIA had been made clear, but it was also found that it had no association as a mediator of leukotrienes (LTC4 and LTB4) in EIA. ..
  4. Ermert L, Dierkes C, Ermert M. Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors. Clin Cancer Res. 2003;9:1604-10 pubmed
    ..This may have major impact on tumor progression and tumor-associated inflammation via an altered prostanoid metabolism with consecutive tumor-associated blood flow distribution. ..
  5. Nagai H, Yakuo I, Nakatomi I, Inagaki N, Koda A. The role of thromboxane A2 (TxA2) in allergic cutaneous reactions and the effect of (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl]-2-propenoic acid hydrochloride (OKY-046), a TxA2 synthetase inhibitor. Prostaglandins Leukot Essent Fatty Acids. 1989;35:125-30 pubmed
    ..These results suggest a slight role of TxA2 in cutaneous allergic reactions in mice and rats and the efficacy of OKY-046 on Type I and II reactions regardless of the inhibition of TxA2 synthetase activity. ..
  6. Ogletree M, Snapper J, Brigham K. Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. Respiration. 1987;51:256-65 pubmed
    ..The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism. ..
  7. Wang L, Tazawa R, Lang A, Wu K. Alternate splicing of human thromboxane synthase mRNA. Arch Biochem Biophys. 1994;315:273-8 pubmed
    ..Alternate splicing of TXS RNA transcript thus may provide a mechanism for limiting cellular biosynthesis of thromboxane A2. ..
  8. Gao Y, Vanhoutte P. Products of cyclooxygenase mediate the responses of the guinea pig trachea to hydrogen peroxide. J Appl Physiol (1985). 1993;74:2105-11 pubmed
    ..These findings demonstrate that the responses of the guinea pig trachea to H2O2 are mediated mainly by products of cyclooxygenase and that the effects of H2O2 are modulated by the epithelium. ..
  9. Vandeplassche G, Hermans C, Somers Y, Van De Werf F, De Clerck F. Combined thromboxane A2 synthase inhibition and prostaglandin endoperoxide receptor antagonism limits myocardial infarct size after mechanical coronary occlusion and reperfusion at doses enhancing coronary thrombolysis by streptokinase. J Am Coll Cardiol. 1993;21:1269-79 pubmed

More Information

Publications117 found, 100 shown here

  1. Sun L, Wahl P, Bilic G, Wuthrich R. CD44-mediated cyclooxygenase-2 expression and thromboxane A2 production in RAW 264.7 macrophages. Inflamm Res. 2001;50:496-9 pubmed
    ..Activation of this pathway results in enhanced TXA2 but not PGE2 production. This leads to an imbalance of the TXA2/PGE2 profile which favors a proinflammatory and vasoconstrictory response. ..
  2. Dogne J, Hanson J, de Leval X, Masereel B, Kolh P, Pirotte B. New developments on thromboxane modulators. Mini Rev Med Chem. 2004;4:649-57 pubmed
    ..Therefore, TXA(2) modulators have been developed for 20 years. This review will highlight the evolution in the field of TXA(2) modulators. ..
  3. Lee K, Jin Y, Lee J, Lim Y, Son D, Lee C, et al. Anti-platelet activity of KR-32560, a novel sodium/hydrogen exchanger-1 inhibitor. Pharmacol Res. 2006;53:265-70 pubmed
    ..Taken together, these observations suggest that the anti-platelet activity of KR-32560 may be mediated by the inhibition of cytoplasmic Ca2+ mobilization and AA liberation. ..
  4. Okumura M, Imanishi M, Okamura M, Hosoi M, Okada N, Konishi Y, et al. Role for thromboxane A2 from glomerular thrombi in nephropathy with type 2 diabetic rats. Life Sci. 2003;72:2695-705 pubmed
    ..When platelet aggregation began, more TXA2 than before was released from the thrombi that formed, and the TXA2 contributed to the progress of nephropathy in this rat model of type 2 diabetes. ..
  5. Moussa O, Riker J, Klein J, Fraig M, Halushka P, Watson D. Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents. Oncogene. 2008;27:55-62 pubmed
    ..In summary, the data support a role for the thromboxane A(2) pathway in the pathogenesis of bladder cancer and the potential utility of modulation of this signaling pathway for cancer chemotherapy. ..
  6. Teraoka H, Kubota A, Dong W, Kawai Y, Yamazaki K, Mori C, et al. Role of the cyclooxygenase 2-thromboxane pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced decrease in mesencephalic vein blood flow in the zebrafish embryo. Toxicol Appl Pharmacol. 2009;234:33-40 pubmed publisher
    ..Finally, gene knock-down of thromboxane A synthase 1 (TBXS) with morpholinos but not by the morpholinos' negative homologs provided significant protection ..
  7. Frøkiaer J, Tågehøj Jensen F, Husted S, Mortensen J, Djurhuus J. Renal blood flow and pelvic pressure after 4 weeks of total upper urinary tract obstruction in the pig. The effect of a TxA2 synthetase inhibitor on active preglomerular vasoconstriction. Urol Res. 1988;16:167-71 pubmed
    ..The continuing increase in pelvic pressure suggested that it was not only a preglomerular vasoconstriction which was responsible for the renal flow reduction, but that there was also a postglomerular vasoconstriction. ..
  8. Gabrielsen A, Qiu H, Bäck M, Hamberg M, Hemdahl A, Agardh H, et al. Thromboxane synthase expression and thromboxane A2 production in the atherosclerotic lesion. J Mol Med (Berl). 2010;88:795-806 pubmed publisher
    ..The findings suggest that intraplaque TXA(2) generation may contribute to the development of atherosclerosis and its thrombotic complications in humans. ..
  9. Wilkes B, Kaplan R, Mento P, Aynedjian H, Macica C, Schlondorff D, et al. Reduced glomerular thromboxane receptor sites and vasoconstrictor responses in diabetic rats. Kidney Int. 1992;41:992-9 pubmed
    ..The abnormalities of glomerular thromboxane receptors are similar to changes in angiotensin II receptors, and suggest a generalized defect in vasoconstrictor receptors in the diabetic kidney. ..
  10. Ishizuka T, Suzuki K, Kawakami M, Kawaguchi Y, Hidaka T, Matsuki Y, et al. DP-1904, a specific inhibitor of thromboxane A2 synthesizing enzyme, suppresses ICAM-1 expression by stimulated vascular endothelial cells. Eur J Pharmacol. 1994;262:113-23 pubmed
    ..These findings suggest that an enhanced expression of thromboxane A2 on human vascular endothelial cells is closely related to the expression of ICAM-1 on the surface of these cells. ..
  11. Fujita M, Seki T, Inada H, Shimizu K, Takahama A, Sano T. Approach to dual-acting platelet activating factor (PAF) receptor antagonist/thromboxane synthase inhibitor (TxSI) based on the link of PAF antagonists and TxSIs. Bioorg Med Chem Lett. 2002;12:341-4 pubmed
    ..A series of compounds (22-36) which possess dual-acting PAF antagonist/TxSI have been generated by the approach of linking the known PAF antagonists and TxSIs, such as Ridogrel (1). ..
  12. Kaku S, Umemura K, Mizuno A, Yano S, Suzuki K, Kawasaki T, et al. Evaluation of a GPIIb/IIIa antagonist YM337 in a primate model of middle cerebral artery thrombosis. Eur J Pharmacol. 1998;345:185-92 pubmed
    ..The novel selective GPIIb/IIIa antagonist YM337 was effective in ameliorating the decrease in patency of the middle cerebral artery and reducing the area of cerebral infarction in monkeys. ..
  13. Miyamoto A, Hashiguchi Y, Obi T, Ishiguro S, Nishio A. Ibuprofen or ozagrel increases NO release and l-nitro arginine induces TXA(2) release from cultured porcine basilar arterial endothelial cells. Vascul Pharmacol. 2007;46:85-90 pubmed
  14. Yang Y, Lee K, Huang Y, Wang Y, Hou M, Lee F, et al. Effects of N-acetylcysteine administration in hepatic microcirculation of rats with biliary cirrhosis. J Hepatol. 2008;49:25-33 pubmed publisher
    ..In NAC-treated cirrhotic rats, the decrease in IHR was mainly caused by its anti-oxidative effect-related prevention of hepatic fibrogenesis associated with the decrease of oxidants-related nitrotyrosilation and improvement of HED. ..
  15. Abraham J, Harrington P, Driver K, Tyrer J, Easton D, Dunning A, et al. Common polymorphisms in the prostaglandin pathway genes and their association with breast cancer susceptibility and survival. Clin Cancer Res. 2009;15:2181-91 pubmed publisher
  16. Simonetti G, Baffa S, Simonetti N. Overcoming imidazole resistance in Escherichia coli. J Chemother. 1996;8:200-6 pubmed
    ..coli imidazole resistance in cultural and direct tests by means of the same non-antimicrobial conditions related to outer membrane functions. ..
  17. Dogne J, Rolin S, de Leval X, Benoit P, Neven P, Delarge J, et al. Pharmacology of the thromboxane receptor antagonist and thromboxane synthase inhibitor BM-531. Cardiovasc Drug Rev. 2001;19:87-96 pubmed
    ..These results suggest that BM-531, which is devoid of the diuretic property of torasemide, can be regarded as a promising antiplatelet agent. ..
  18. Tysnes B, Mahesparan R. Biological mechanisms of glioma invasion and potential therapeutic targets. J Neurooncol. 2001;53:129-47 pubmed
    ..This will hopefully render promising new therapeutic targets for gliomas. ..
  19. Welch W, Wilcox C, Dunbar K. Modulation of renin by thromboxane: studies with thromboxane synthase inhibitor, receptor antagonists, and mimetic. Am J Physiol. 1989;257:F554-60 pubmed
  20. Yokoyama Y, Kawai T, Kawai S, Kitagawa T, Watanabe K, Kawai K, et al. Up-regulated thromboxane production in the rat liver with biliary obstruction does not contribute to promote hepatic injury. Shock. 2008;29:688-91 pubmed
    ..These results indicated that despite a highly increased production in the liver, TXA2 is not directly related to the hepatic injury in BDL rats. ..
  21. Fujimura M, Sakamoto S, Matsuda T. Attenuating effect of a thromboxane synthetase inhibitor (OKY-046) on bronchial responsiveness to methacholine is specific to bronchial asthma. Chest. 1990;98:656-60 pubmed
    ..Further studies using thromboxane A2 receptor antagonists are needed to confirm the conclusion. ..
  22. Galipeau D, Arikawa E, Sekirov I, McNeill J. Chronic thromboxane synthase inhibition prevents fructose-induced hypertension. Hypertension. 2001;38:872-6 pubmed
    ..Based on these data, we conclude that the potent vasoconstrictor thromboxane is involved in the link between hyperinsulinemia/insulin resistance and hypertension. ..
  23. Baber S, Deng W, Rodriguez J, Master R, Bivalacqua T, Hyman A, et al. Vasoactive prostanoids are generated from arachidonic acid by COX-1 and COX-2 in the mouse. Am J Physiol Heart Circ Physiol. 2005;289:H1476-87 pubmed
    ..The present data suggest that COX-1- or COX-2-derived prostanoids do not modulate responses to angiotensin II or other vasoactive agents and that prostanoid responses are similar in CD-1 and C57BL/6 and in male and female mice. ..
  24. Peltason L, Bajorath J. SAR index: quantifying the nature of structure-activity relationships. J Med Chem. 2007;50:5571-8 pubmed
    ..Given a set of active compounds and their potency values, SAR Index calculations can estimate how likely it is to identify structurally distinct molecules having similar activity. ..
  25. De La Cruz J, Moreno A, Ruiz Ruiz M, Sanchez De La Cuesta F. Effect of DT-TX 30, a combined thromboxane synthase inhibitor and thromboxane receptor antagonist, on retinal vascularity in experimental diabetes mellitus. Thromb Res. 2000;97:125-31 pubmed
    ..In conclusion, the antagonism of thromboxane receptors may be an important additional effect to the inhibition of thromboxane synthase in the prevention of ischemic retinal lesions in experimental diabetes. ..
  26. Ito Y, Katagiri H, Ishii K, Kakita A, Hayashi I, Majima M. Effects of selective cyclooxygenase inhibitors on ischemia/reperfusion-induced hepatic microcirculatory dysfunction in mice. Eur Surg Res. 2003;35:408-16 pubmed
    ..These results suggest that COX-1 and COX-2 contribute to I/R-induced hepatic microvascular and hepatocellular injury partly through TNF-alpha production, and that TXs derived from COX are partly responsible for I/R-induced liver injury. ..
  27. Martorell A, Sagredo A, Aras Lopez R, Balfagon G, Ferrer M. Ovariectomy increases the formation of prostanoids and modulates their role in acetylcholine-induced relaxation and nitric oxide release in the rat aorta. Cardiovasc Res. 2009;84:300-8 pubmed publisher
  28. Hall E, Townsend G, Linthicum D, Frasier Scott K. Substrate inactivation of lung thromboxane synthase preferentially decreases thromboxane A2 production. Prostaglandins Leukot Essent Fatty Acids. 1991;42:31-7 pubmed
    ..Thus the substrate inactivation of the enzyme does not require the production of TXA2. Our data suggests that the synthesis of TXA2 and HHT can be differentially inactivated and may occur at different sites on the enzyme. ..
  29. Mestel F, Oetliker O, Beck E, Felix R, Imbach P, Wagner H. Severe bleeding associated with defective thromboxane synthetase. Lancet. 1980;1:157 pubmed
  30. Hanson J, Rolin S, Reynaud D, Qiao N, Kelley L, Reid H, et al. In vitro and in vivo pharmacological characterization of BM-613 [N-n-pentyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea], a novel dual thromboxane synthase inhibitor and thromboxane receptor antagonist. J Pharmacol Exp Ther. 2005;313:293-301 pubmed
    ..These results suggest that BM-613 could be a potential therapeutic drug for thrombotic disorders. ..
  31. Kuhn D, Stauffer J, Gaydos L, Lacey S, Demers L. An inhibitor of thromboxane production attenuates tumor necrosis factor release by activated human alveolar macrophages. Prostaglandins. 1993;46:195-205 pubmed
  32. Su M, Chen W, Lo T, Wu T. Ionic mechanisms for the antiarrhythmic action of cinnamophilin in rat heart. J Biomed Sci. 1999;6:376-86 pubmed
    ..These results indicate that the inhibition of I(Na), I(Ca) and I(to) may contribute to the antiarrhythmic activity of Cinn against ischemia-reperfusion arrhythmia. ..
  33. Lee S, Morgan G, Harris N. Ozagrel reverses streptozotocin-induced constriction of arterioles in rat retina. Microvasc Res. 2008;76:217-23 pubmed publisher
    ..In summary, the results suggest that thromboxane mediates localized, venule-dependent arteriolar constriction induced by streptozotocin-induced diabetes in rats. ..
  34. Zaitsu M, Hamasaki Y, Tashiro K, Matsuo M, Ichimaru T, Fujita I, et al. Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease. J Infect Dis. 2000;181:1101-9 pubmed
    ..Ulinastatin treatment is possibly an additional therapeutic approach to Kawasaki disease. ..
  35. Yoshimi Y, Fujimura M, Myou S, Tachibana H, Hirose T. Effect of thromboxane A2 (TXA2) synthase inhibitor and TXA2 receptor antagonist alone and in combination on antigen-induced bronchoconstriction in guinea pigs. Prostaglandins Other Lipid Mediat. 2001;65:1-9 pubmed
    ..These findings suggest that other prostanoids such as PGE2, PGI2, PGD2 and PGF2alpha may not take an important role in the antiasthmatic effects of TXA2 modifiers. ..
  36. Martinez G, Walker K, Hirschfeld D, Maloney P, Yang D, Rosenkranz R. [(1H-imidazol-1-yl)methyl]- and [(3-pyridinyl)methyl]pyrroles as thromboxane synthetase inhibitors. J Med Chem. 1989;32:890-7 pubmed
    ..Although serum and urinary TXB2 levels in rats were found to be lowered during this study by 10b, the levels of urinary protein excretion remained comparable to that of the control group. ..
  37. Howes L, James M, Florin T, Walker C. Nv-52: a novel thromboxane synthase inhibitor for the treatment of inflammatory bowel disease. Expert Opin Investig Drugs. 2007;16:1255-66 pubmed
    ..NV-52 is well absorbed and a single dose of 400 mg p.o. produced a plasma concentration that is comparable with the concentrations that have been shown to produce significant TXS inhibition in vitro. ..
  38. Hornberger W, Patscheke H. Prostaglandin H2 in human platelet activation: coactivator and substitute for thromboxane A2. Prog Clin Biol Res. 1989;301:315-9 pubmed
    ..That is why thromboxane synthase inhibitors in PRP and at a physiological HSA concentration do not augment platelet activation. (4) HSA promotes the formation of inhibitory PGD2 at the expense of agonistic PGH2. ..
  39. Zhang L, Xiao H, Schultz R, Shen R. Genomic organization, chromosomal localization, and expression of the murine thromboxane synthase gene. Genomics. 1997;45:519-28 pubmed
    ..These studies provide the genetic tools and information for TS research in mice, which should expedite understanding of the genetic contribution of TS in normal physiology as well as in disease states. ..
  40. Myou S, Fujimura M, Nishi K, Kita T, Kurashima K, Tachibana H, et al. Effect of ozagrel hydrochloride, a thromboxane synthetase inhibitor, on alcoholic beverage-induced bronchoconstriction in asthmatic patients. Prostaglandins Leukot Essent Fatty Acids. 2002;66:397-401 pubmed
    ..We conclude that TXA(2) is not involved in alcoholic beverage-induced bronchoconstriction. ..
  41. Ruan K, Milfeld K, Kulmacz R, Wu K. Comparison of the construction of a 3-D model for human thromboxane synthase using P450cam and BM-3 as templates: implications for the substrate binding pocket. Protein Eng. 1994;7:1345-51 pubmed
    ..Comparison of the TXAS model based on P450BM-3 with another TXAS model based on the P450cam structure indicated that P450BM-3 is a more suitable template for homology modeling of TXAS. ..
  42. Baek S, Lee K, Shen R. Genomic structure and polymorphism of the human thromboxane synthase-encoding gene. Gene. 1996;173:251-6 pubmed
    ..A dinucleotide (CA) repetitive sequence identified in the ninth intron of the gene exhibits allelic polymorphism. At least four distinctive alleles, containing from 13 to 20 copies of the CA repeats, have been detected. ..
  43. Kleber A, Hartmann R, Jose J. No effect of thromboxane A2 on the attachment of tumor cell lines MDA MB 231, DU145, and U937 to the basement membrane in an in-vitro model. J Cancer Res Clin Oncol. 2001;127:751-4 pubmed
    ..These data indicate that TxA2 might not be involved in the attachment of tumor cell lines to the basement membrane. ..
  44. Park S, Park B, Park J, Lee T, Sung K, Lee Y, et al. Association of polymorphisms in thromboxane A2 receptor and thromboxane A synthase 1 with cerebral infarction in a Korean population. BMB Rep. 2009;42:200-5 pubmed
    ..0003 and 0.005, respectively). These results suggest specific TBXAS1 gene polymorphisms may be a useful marker for development of cerebral infarction, especially SAO type in Korean population. ..
  45. Imura Y, Terashita Z, Shibouta Y, Nishikawa K. The thromboxane A2/prostaglandin endoperoxide receptor antagonist activity of CV-4151, a thromboxane A2 synthetase inhibitor. Eur J Pharmacol. 1988;147:359-65 pubmed
    ..These results show that CV-4151 has a distinct TXA2/PGH2 receptor antagonist effect, and that this effect together with its inhibition of TXA2 synthetase could be important for the pharmacological action of this compound. ..
  46. Yokoyama C, Miyata A, Suzuki K, Nishikawa Y, Yoshimoto T, Yamamoto S, et al. Expression of human thromboxane synthase using a baculovirus system. FEBS Lett. 1993;318:91-4 pubmed
    ..Both conversions of PGH2 to TXA2 and HHT by the expressed TX synthase were completely inhibited by a specific TX synthase inhibitor, OKY-046 (5 microM). ..
  47. Obase Y, Shimoda T, Matsuo N, Matsuse H, Asai S, Kohno S. Effects of cysteinyl-leukotriene receptor antagonist, thromboxane A2 receptor antagonist, and thromboxane A2 synthetase inhibitor on antigen-induced bronchoconstriction in patients with asthma. Chest. 1998;114:1028-32 pubmed
    ..LT might play a more important role in the pathogenesis of asthma than TXA2. Our data showed that measurement of blood levels of chemical mediators is not useful in identifying the pathogenic mechanisms of asthma. ..
  48. Mayeux P, Kadowitz P, McNamara D. Differential effects of ibuprofen, indomethacin, and meclofenamate on prostaglandin endoperoxide H2 metabolism. Mol Cell Biochem. 1989;87:41-6 pubmed
    ..This action may affect the physiologic consequences of the exchange of PGH2 between cells. The data further indicate that indomethacin has the potential for use as a tool to specifically attenuate PGI2 synthase activity in vitro. ..
  49. Shams H, Peskar B, Scheid P. Acid infusion elicits thromboxane A2-mediated effects on respiration and pulmonary hemodynamics in the cat. Respir Physiol. 1988;71:169-83 pubmed
    ..The fact that these effects cannot be repeated within the same animal is due to a lack in TX release but not to a loss of responsiveness of the TX receptors in the lung. ..
  50. Hably C, Györváry Z, Bartha J. Changes of organ blood flow and cardiac output after imidazole administration. Acta Physiol Hung. 1994;82:163-73 pubmed
    ..The results suggest that TXA2 does not play a definite role in maintaining the a) vascular tone (blood flow) of different organs b) intrarenal hemodynamics (salt and water excretion) in normovolemic rats. ..
  51. Sakai H, Sato T, Hamada N, Yasue M, Ikari A, Kakinoki B, et al. Thromboxane A2, released by the anti-tumour drug irinotecan, is a novel stimulator of Cl- secretion in isolated rat colon. J Physiol. 1997;505 ( Pt 1):133-44 pubmed
    ..5. We conclude, therefore, that the irinotecan-induced endogenous TXA2 is a novel stimulant of the Cl- secretion from the crypt cells of distal colon. ..
  52. Carty E, Nickols C, Feakins R, Rampton D. Thromboxane synthase immunohistochemistry in inflammatory bowel disease. J Clin Pathol. 2002;55:367-70 pubmed
    ..It is possible that this results in increased thromboxane synthesis, which may in turn contribute to mucosal inflammation and intramucosal thrombogenesis. ..
  53. Herrera M, Bueno R, de Sotomayor M, Pérez Guerrero C, Vazquez C, Marhuenda E. Endothelium-dependent vasorelaxation induced by L-carnitine in isolated aorta from normotensive and hypertensive rats. J Pharm Pharmacol. 2002;54:1423-7 pubmed
  54. Traupe T, Lang M, Goettsch W, Munter K, Morawietz H, Vetter W, et al. Obesity increases prostanoid-mediated vasoconstriction and vascular thromboxane receptor gene expression. J Hypertens. 2002;20:2239-45 pubmed
    ..These changes are likely to promote the development of vascular disease, hypertension and thrombosis associated with obesity. ..
  55. Son D, Cho M, Jin Y, Kim S, Park Y, Lee S, et al. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids. 2004;71:25-31 pubmed
    ..These results suggest that the antiplatelet activity of GTC may be due to the inhibition of TXA2 formation through the inhibition of AA liberation and TXA2 synthase. ..
  56. Reiter R, Peskar B, Sinzinger H. Defects in the prostaglandin system--what is known?. Prostaglandins Leukot Essent Fatty Acids. 2004;71:347-50 pubmed
    ..All interested people are invited to join. ..
  57. Obata H, Sakai Y, Ohnishi S, Takeshita S, Mori H, Kodama M, et al. Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Am J Respir Crit Care Med. 2008;177:195-201 pubmed
    ..A single injection of ONO-1301MS resulted in sustained activity for 3 weeks, and attenuated pulmonary hypertension, partly through its antiproliferative effect on vascular smooth muscle cells via inhibition of ERK phosphorylation. ..
  58. Brownlie R, Brownrigg N, Butcher H, Garcia R, Jessup R, Lee V, et al. ZD1542, a potent thromboxane A2 synthase inhibitor and receptor antagonist in vitro. Br J Pharmacol. 1993;110:1600-6 pubmed
    ..6. In conclusion, the present study demonstrates that ZD1542 is a drug that exhibits both potent,selective TXS inhibition and TXA2 receptor antagonism. ..
  59. Ihara E, Hirano K, Derkach D, Nishimura J, Nawata H, Kanaide H. The mechanism of bradykinin-induced endothelium-dependent contraction and relaxation in the porcine interlobar renal artery. Br J Pharmacol. 2000;129:943-52 pubmed
    ..Both TXA(2) and PGH(2) were involved in the bradykinin-induced contraction. The initial relaxation was mediated by nitric oxide and hyperpolarizing factors while the sustained relaxation depended on nitric oxide. ..
  60. Gupte S, Okada T, Tateyama M, Ochi R. Activation of TxA2/PGH2 receptors and protein kinase C contribute to coronary dysfunction in superoxide treated rat hearts. J Mol Cell Cardiol. 2000;32:937-46 pubmed
    ..PDBu enhanced the post-O2- vasoconstriction. We conclude that O2--induced coronary vasoconstriction is initially mediated by TP receptors, but activation of PKC sustains the response. ..
  61. Onguru O, Scheithauer B, Kovacs K, Vidal S, Jin L, Zhang S, et al. Analysis of Cox-2 and thromboxane synthase expression in pituitary adenomas and carcinomas. Endocr Pathol. 2004;15:17-27 pubmed
    ..In summary, TBXAS appears to be one of the up-regulated downstream enzymes of Cox metabolism in pituitary tumors. Both Cox-2 and TBXAS may play an important role in pituitary tumor development and progression. ..
  62. Ghuysen A, Dogne J, Chiap P, Rolin S, Masereel B, Lambermont B, et al. Pharmacological profile and therapeutic potential of BM-573, a combined thromboxane receptor antagonist and synthase inhibitor. Cardiovasc Drug Rev. 2005;23:1-14 pubmed
    ..These results suggest that BM-573 should be viewed as a promising therapeutic agent in the treatment of pulmonary hypertension and syndromes associated with platelet activation. ..
  63. Ulrich C, Carlson C, Sibert J, Poole E, Yu J, Wang L, et al. Thromboxane synthase (TBXAS1) polymorphisms in African-American and Caucasian populations: evidence for selective pressure. Hum Mutat. 2005;26:394-5 pubmed
    ..Given the evolutionary evidence, these variants may be functional and therefore of relevance for disease endpoints related to inflammation and angiogenesis, as well as for the pharmacogenetics of non-steroidal anti-inflammatory drugs. ..
  64. Moussa O, Yordy J, Abol Enein H, Sinha D, Bissada N, Halushka P, et al. Prognostic and functional significance of thromboxane synthase gene overexpression in invasive bladder cancer. Cancer Res. 2005;65:11581-7 pubmed
  65. Onguru O, Casey M, Kajita S, Nakamura N, Lloyd R. Cyclooxygenase-2 and thromboxane synthase in non-endocrine and endocrine tumors: a review. Endocr Pathol. 2005;16:253-77 pubmed
    ..The accumulating evidence points to an increasingly important role of COX-2 and TS in tumor progression and metastasis. ..
  66. Wang L, Ohashi K, Wu K. Isolation of partial complementary DNA encoding human thromboxane synthase. Biochem Biophys Res Commun. 1991;177:286-91 pubmed
    ..The longest cDNA thus obtained was 687 base pairs in length. Amino acid sequences deduced from the cDNA contained all three peptide sequences reported, confirming the authenticity of the cDNA clone. ..
  67. el Kashef H, Catravas J. Effects of arachidonic acid in the rabbit pulmonary and systemic vascular beds in vivo. Pharmacology. 1990;40:60-8 pubmed
  68. Mehta J, Lawson D, Nichols W. Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A. Am J Physiol. 1989;257:H1240-6 pubmed
    ..Thus SOD and U 63557A protect against loss of endothelium-mediated vascular relaxation by LTD4 and ACh after coronary occlusion and reperfusion. ..
  69. Tripp C, Needleman P, Kassab J, Weinstock J. Macrophages isolated from liver granulomas of murine Schistosoma mansoni synthesize predominantly TxA2 during the acute and chronic phases of infection. J Immunol. 1988;140:3140-3 pubmed
    ..These data indicate that the predominant arachidonate enzymatic activity in these cells is thromboxane synthase. ..
  70. Leeder J, Lu X, Timsit Y, Gaedigk A. Non-monooxygenase cytochromes P450 as potential human autoantigens in anticonvulsant hypersensitivity reactions. Pharmacogenetics. 1998;8:211-25 pubmed
  71. Maruyama J, Yokochi A, Maruyama K, Nosaka S. Acetylcholine-induced endothelium-derived contracting factor in hypoxic pulmonary hypertensive rats. J Appl Physiol (1985). 1999;86:1687-95 pubmed
    ..These findings suggest that PGH2 produced from the conduit PAs of rats with chronic hypoxic PH may be the endothelium-derived contracting factor responsible for the impairment of ACh-mediated vasorelaxation...
  72. Gonzales R, Ghaffari A, Duckles S, Krause D. Testosterone treatment increases thromboxane function in rat cerebral arteries. Am J Physiol Heart Circ Physiol. 2005;289:H578-85 pubmed
    ..The effect of in vivo testosterone on cerebrovascular TxA2 synthase, observed here after chronic hormone administration, may contribute to the risk of vasospasm and thrombosis related to cerebrovascular disease. ..
  73. Vaughan J, Walsh S, Ford G. Thromboxane mediates neutrophil superoxide production in pregnancy. Am J Obstet Gynecol. 2006;195:1415-20 pubmed
    ..NS-398 inhibits neutrophil superoxide generation as effectively as aspirin, suggesting that cyclooxygenase-2 plays an important role in neutrophil superoxide production mediated by thromboxane. ..
  74. McNeish A, Garland C. Thromboxane A2 inhibition of SKCa after NO synthase block in rat middle cerebral artery. Br J Pharmacol. 2007;151:441-9 pubmed
    ..Either antagonism of TP receptors or block of thromboxane synthase restores an input through SK(Ca). These data indicate that NO normally enables SK(Ca) activity in rat middle cerebral arteries. ..
  75. Bhagwat S, Gude C, Boswell C, Contardo N, Cohen D, Dotson R, et al. Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-(3-(3-pyridinyl) propyl)octanoic acid and analogs. J Med Chem. 1992;35:4373-83 pubmed
    ..Compounds 10a, 20, and 33 potently inhibited arachidonic acid induced bronchoconstriction in guinea pigs. ..
  76. Hornberger W, Patscheke H. Transient concentrations and agonist potency of PGH2 in platelet activation by endogenous arachidonate. Eicosanoids. 1989;2:241-8 pubmed
    ..The TXA2/PGH2 receptor antagonist daltroban suppressed the agonistic effects of endogenous or added PGH2, demonstrating that the TXA2/PGH2 receptor was its site of action.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  77. Wood C, Purinton S, Cudd T. Immunoreactive thromboxane synthase is measurable in ovine fetal hypothalamus as early as 86 days' gestation. Prostaglandins. 1997;54:569-79 pubmed
    ..We conclude that immunoreactive TxS is present in the fetal brain throughout the last half of fetal gestation, but that the significance of multiple molecular weight forms is not clear. ..
  78. So S, Li D, Ruan K. Identification of the substrate interaction site in the N-terminal membrane anchor segment of thromboxane A2 synthase by determination of its substrate analog conformational changes using high resolution NMR technique. J Biol Chem. 2000;275:40679-85 pubmed
    ..The combination of the structural information of and was able to simulate a solution structure of the unstable TXAS and PGIS substrate, PGH(2). ..
  79. Sheu J, Hsiao G, Lin W, Chen T, Chien Y, Lin C, et al. Mechanisms involved in agonist-induced hyperaggregability of platelets from normal pregnancy. J Biomed Sci. 2002;9:17-25 pubmed
  80. Brault S, Martinez Bermudez A, Marrache A, Gobeil F, Hou X, Beauchamp M, et al. Selective neuromicrovascular endothelial cell death by 8-Iso-prostaglandin F2alpha: possible role in ischemic brain injury. Stroke. 2003;34:776-82 pubmed
    ..These data disclose a novel action of 8-iso-PGF2alpha involving TXA2 in oxidant stress-induced cerebral microvascular injury and brain damage. ..
  81. Dassesse T, de Leval X, de Leval L, Pirotte B, Castronovo V, Waltregny D. Activation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage. Eur Urol. 2006;50:1021-31; discussion 1031 pubmed
    ..Our study is the first to examine simultaneously all key proteins involved in this pathway including TXA(2) receptors and results suggest that the TXA(2) pathway may be a potential target for PCa prevention/therapy. ..
  82. Wright W, McElhatten R, Harris N. Expression of thromboxane synthase and the thromboxane-prostanoid receptor in the mouse and rat retina. Exp Eye Res. 2009;89:532-7 pubmed publisher
  83. Namba T, Narumiya S. [Thromboxane A2 receptor; structure, function and tissue distribution]. Nihon Rinsho. 1993;51:233-40 pubmed
    ..Further progress on understanding of thromboxane A2 and development of effective drugs may be made on the basis of these findings. ..
  84. Tanaka M, Natori M, Ishimoto H, Miyakoshi K, Miyazaki T, Kobayashi T, et al. Effects of a thromboxane synthetase inhibitor (OKY-046) in an ischemia-reperfusion model of intrauterine growth retardation in Sprague-Dawley rats. Biol Neonate. 1997;72:181-6 pubmed
    ..The ratio of 6-keto-PGF1 alpha to TXB2 was significantly increased in the OKY-046-treated group. We conclude that the action of TXA2 might play a salient role in our model. ..
  85. Geiger J. Inhibitors of platelet signal transduction as anti-aggregatory drugs. Expert Opin Investig Drugs. 2001;10:865-90 pubmed
    ..While several of the novel anti-aggregatory drugs were disappointing in clinical studies combinations of drugs with different effector enzymes showed potent antithrombotic efficacy. ..
  86. Husted D, Upshaw J, Gridley K, Wood C. Cellular localization of thromboxane synthase in ovine spinal cord and hindbrain. Brain Res. 2003;971:107-15 pubmed
    ..We conclude that, consistent with physiological evidence, thromboxane synthase is present in brain regions which are important for afferent and efferent cardiovascular signaling. ..
  87. Michaux C, Dogne J, Rolin S, Masereel B, Wouters J, Durant F. A pharmacophore model for sulphonyl-urea (-cyanoguanidine) compounds with dual action, thromboxane receptor antagonists and thromboxane synthase inhibitors. Eur J Med Chem. 2003;38:703-10 pubmed
    ..Such a model could be used to design new leads possessing the same pharmacological profile and to improve the activity of our compounds. ..
  88. Ghuysen A, Lambermont B, Dogne J, Kolh P, Tchana Sato V, Morimont P, et al. Effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea], a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, in a porcine model of acute pulmonary embolism. J Pharmacol Exp Ther. 2004;310:964-72 pubmed
    ..We conclude that in this animal model of acute pulmonary embolism, infusion of BM-573 reduced pulmonary vasoconstriction. As a result, right ventricular-vascular coupling values were maintained at a maximal efficiency level. ..
  89. Li M, Kuo L, Stallone J. Estrogen potentiates constrictor prostanoid function in female rat aorta by upregulation of cyclooxygenase-2 and thromboxane pathway expression. Am J Physiol Heart Circ Physiol. 2008;294:H2444-55 pubmed publisher
    ..These data reveal that estrogen enhances constrictor prostanoid function in female rat aorta by upregulating the expression of COX-2 and TxS in both Endo and VSM and by upregulating the expression of TP in VSM. ..
  90. Lemaitre R, Rice K, Marciante K, Bis J, Lumley T, Wiggins K, et al. Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke. Atherosclerosis. 2009;204:e58-63 pubmed publisher
    ..03). Study results suggest that variation in TBXAS1 and PTGIS may influence MI risk, and carriers of rs20417C allele might derive greater benefits from aspirin use in primary prevention. ..
  91. Horton A, Wood J. Effects of inhibitors of phospholipase A2, cyclooxygenase and thromboxane synthetase on paracetamol hepatotoxicity in the rat. Eicosanoids. 1989;2:123-9 pubmed
    ..The data presented support the proposed sequence of events in which A.A., released from membrane phospholipids by Ca2(+)-activated PLA2, acts as substrate for the synthesis of cytodestructive eicosanoids. ..
  92. Arakawa H, Kawikova I, Skoogh B, Hayes J, Morikawa A, Lofdahl C, et al. Role of arachidonic acid metabolites in airway responses induced by trimellitic anhydride in actively sensitized guinea pigs. Am Rev Respir Dis. 1993;147:1116-21 pubmed
    ..Indomethacin, OKY-046 and ketanserin did not significantly affect the extravasation of dye into the airway tissue.(ABSTRACT TRUNCATED AT 250 WORDS) ..