thromboxane receptors


Summary: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.

Top Publications

  1. Offermanns S, Laugwitz K, Spicher K, Schultz G. G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets. Proc Natl Acad Sci U S A. 1994;91:504-8 pubmed
    ..Our results provide evidence that G12 and G13 play a functional role in transmembrane signal transduction and suggest that both proteins are involved in pathways leading to platelet activation. ..
  2. Yan W, Ding Y, Tai H. 14-3-3zeta interacts with human thromboxane receptors and is involved in the agonist-induced activation of the extracellular-signal-regulated kinase. Biochem Pharmacol. 2006;71:624-33 pubmed
  3. Thomas D, Rocha P, Nataraj C, Robinson L, Spurney R, Koller B, et al. Proinflammatory actions of thromboxane receptors to enhance cellular immune responses. J Immunol. 2003;171:6389-95 pubmed
    ..Specific inhibition of the TP receptor may provide a more precise approach to limit inflammation without some of the untoward effects associated with NSAIDs. ..
  4. Mueed I, Tazzeo T, Liu C, Pertens E, Zhang Y, Cybulski I, et al. Isoprostanes constrict human radial artery by stimulation of thromboxane receptors, Ca2+ release, and RhoA activation. J Thorac Cardiovasc Surg. 2008;135:131-8 pubmed publisher
    ..Responses were mediated through thromboxane receptors because they were sensitive to ICI-192605...
  5. Delannoy E, Courtois A, Freund Michel V, Leblais V, Marthan R, Muller B. Hypoxia-induced hyperreactivity of pulmonary arteries: role of cyclooxygenase-2, isoprostanes, and thromboxane receptors. Cardiovasc Res. 2010;85:582-92 pubmed publisher
    ..COX-2-dependent production of 8-iso-PGF2alpha, by activating TP receptors, participates in hypoxia-induced hyperreactivity of pulmonary arteries. ..
  6. Ohkubo S, Nakahata N, Ohizumi Y. Thromboxane A2-mediated shape change: independent of Gq-phospholipase C--Ca2+ pathway in rabbit platelets. Br J Pharmacol. 1996;117:1095-104 pubmed
  7. Belhassen L, Pelle G, Dubois Rande J, Adnot S. Improved endothelial function by the thromboxane A2 receptor antagonist S 18886 in patients with coronary artery disease treated with aspirin. J Am Coll Cardiol. 2003;41:1198-204 pubmed
    ..These results suggest that release of endogenous agonists of TP receptors may contribute to endothelial dysfunction, despite aspirin treatment, in patients with atherosclerosis. ..
  8. Worth N, Berry C, Thomas A, Campbell J. S18886, a selective TP receptor antagonist, inhibits development of atherosclerosis in rabbits. Atherosclerosis. 2005;183:65-73 pubmed
  9. Shenker A, Goldsmith P, Unson C, Spiegel A. The G protein coupled to the thromboxane A2 receptor in human platelets is a member of the novel Gq family. J Biol Chem. 1991;266:9309-13 pubmed
    ..Pretreatment of membranes with QL, but not QN or AS, caused marked inhibition of TXA2 receptor-stimulated GTPase. This identifies the G protein coupled to human platelet TXA2 receptors as a member of the novel Gq family. ..

More Information


  1. Rolin S, Dogne J, Michaux C, Delarge J, Masereel B. Activity of a novel dual thromboxane A(2)receptor antagonist and thromboxane synthase inhibitor (BM-573) on platelet function and isolated smooth muscles. Prostaglandins Leukot Essent Fatty Acids. 2001;65:67-72 pubmed
    ..7 nM) contracted by U-46619. BM-573 (1 microM) completely reduced the platelet production of TXB(2)induced by arachidonic acid. Finally, BM-573 (30 mg/kg, per os) lost the diuretic properties of torasemide in rats. ..
  2. Nakamura K, Yokotani K. Presynaptic BK type Ca(2+)-activated K(+) channels are involved in prostanoid TP receptor-mediated inhibition of noradrenaline release from the rat gastric sympathetic nerves. Eur J Pharmacol. 2010;629:111-7 pubmed publisher
    ..These results suggest that BK type Ca(2+)-activated K(+) channels are involved in prostanoid TP receptor-mediated inhibition of electrically evoked noradrenaline release from the gastric sympathetic nerve terminals in rats. ..
  3. Schuster D, Sandiford P, Stephenson A. Thromboxane receptor stimulation/inhibition and perfusion redistribution after acute lung injury. J Appl Physiol (1985). 1993;75:2069-78 pubmed
    ..Thus, although the Tx mimetic produced the same amount of PR as meclofenamate, Tx inhibition did not prevent PR after meclofenamate. Therefore, the ratio of Tx to prostacyclin per se is not the critical determinant of PR. ..
  4. Tabeling C, Noe E, Naujoks J, Doehn J, Hippenstiel S, Opitz B, et al. PKCα Deficiency in Mice Is Associated with Pulmonary Vascular Hyperresponsiveness to Thromboxane A2 and Increased Thromboxane Receptor Expression. J Vasc Res. 2015;52:279-88 pubmed publisher
    ..To conclude, PKCα regulates ET-1-induced pulmonary vasoconstriction. However, PKCα deficiency leads to pulmonary vascular hyperresponsiveness to TXA2, possibly via increased pulmonary arterial TP receptor expression. ..
  5. Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest. 2006;116:3211-9 pubmed
    ..The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI. ..
  6. Losonczy G, Mucha I, DiPirro J, Sweeney J, Brown G, Brentjens J, et al. The effect of pregnancy on the response to the TxA2/PGH2 analogue U-46619 in rabbits. Am J Physiol. 1993;265:R772-80 pubmed
    ..001). This could not be attributed to reduced affinity or number of platelet thromboxane receptors. The data indicate that U-46619 induces a fall of arterial pressure simultaneous with intravascular ..
  7. Gelosa P, Ballerio R, Banfi C, Nobili E, Gianella A, Pignieri A, et al. Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, increases survival in stroke-prone rats by preventing systemic inflammation and endothelial dysfunction: comparison with aspirin and rosuvastatin. J Pharmacol Exp Ther. 2010;334:199-205 pubmed publisher
    ..These data support clinical development of terutroban in the prevention of cerebrovascular and cardiovascular complications of atherothrombosis. ..
  8. Arakida Y, Ohga K, Suwa K, Yokota M, Miyata K, Yamada T, et al. Effects of lipid mediator antagonists on predominant mediator-controlled asthmatic reactions in passively sensitized guinea pigs. J Pharmacol Exp Ther. 1999;290:1285-91 pubmed
    ..Therefore, broad-acting compounds such as YM158 are expected to have antiasthmatic efficacies in a broader class of asthmatic patients than single-acting drugs. ..
  9. Shams G, Romstedt K, Lust L, Clark M, Miller D, Feller D. Beta-adrenergic receptor and platelet inhibitory activities of a new series of trimetoquinol and related benzazepine analogs. Gen Pharmacol. 1997;28:323-30 pubmed
    ..4. The selective blockade of this pathway by these compounds suggests that they may represent a new and novel class of antiplatelet drugs. ..
  10. Solini A, Rossi C, Duranti E, Taddei S, Natali A, Virdis A. Saxagliptin prevents vascular remodeling and oxidative stress in db/db mice. Role of endothelial nitric oxide synthase uncoupling and cyclooxygenase. Vascul Pharmacol. 2016;76:62-71 pubmed publisher
  11. Schenk J, Radziwon P, Fellier H, Breddin H. Antiplatelet and anticoagulant effects of "HN-11 500," a selective thromboxane receptor antagonist. Thromb Res. 2001;103:79-91 pubmed
  12. Cracowski J, Camus L, Durand T, Devillier P, Guy A, Hardy G, et al. Response of rat thoracic aorta to F(2)-isoprostane metabolites. J Cardiovasc Pharmacol. 2002;39:396-403 pubmed
    ..In contrast, 15-keto-15-F(2t)-IsoP mediates contraction through activation of TP-receptors, probably as a partial agonist, and induces a weak endothelium-independent relaxation at high concentrations. ..
  13. Vysniauskiene I, Allemann R, Flammer J, Haefliger I. Vasoactive responses of U46619, PGF2alpha, latanoprost, and travoprost in isolated porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2006;47:295-8 pubmed
    ..05-0.001) either by SQ 29548 or AL-8810. In isolated porcine ciliary arteries, all prostanoids tested induced contractions. Among them, travoprost appeared to be the least potent and U46619 the most efficient. ..
  14. Dorn G, Becker M. Thromboxane A2 stimulated signal transduction in vascular smooth muscle. J Pharmacol Exp Ther. 1993;265:447-56 pubmed
  15. Walsh S, Wang Y, Killian A. AA-2414, an antioxidant and thromboxane receptor blocker, completely inhibits peroxide-induced vasoconstriction in the human placenta. J Pharmacol Exp Ther. 1999;290:220-6 pubmed
  16. Ziyyat A, Zhang B, Benzoni D. Interactions between nitric oxide and prostanoids in isolated perfused kidneys of the rat. Br J Pharmacol. 1996;119:388-92 pubmed
  17. Sheridan B, McIntyre R, Meldrum D, Cleveland J, Agrafojo J, Banerjee A, et al. Microtubules regulate pulmonary vascular smooth muscle contraction. J Surg Res. 1996;62:284-7 pubmed
    ..These findings suggest that microtubules have an important role in the response of pulmonary vascular smooth muscle to vasoconstricting agonists. ..
  18. Michaux C, Dogne J, Norberg B, Durant F, Masereel B. N-tert-butyl-N'-(2-cyclohexylamino-5-nitrobenzenesulfonyl)urea, BM531, a dual-acting agent for thromboxane receptor antagonism and thromboxane synthase inhibition. Acta Crystallogr C. 2002;58:o621-3 pubmed
    ..We report here the X-ray crystal structure determination of the compound. ..
  19. Nakahata N, Takano H, Ohizumi Y. Thromboxane A2-induced phosphatidylcholine hydrolysis in porcine vascular smooth muscle cells. Eur J Pharmacol. 1999;374:157-60 pubmed
    ..These results suggest that the thromboxane A2 receptor in vascular smooth muscles is functionally coupled to phosphatidylcholine-specific phospholipase C to yield diacylglycerol. ..
  20. Yokoyama K, Kudo I, Nakamura H, Inoue K. A possible role for extracellular bicarbonate in U-46619-induced rat platelet aggregation. Thromb Res. 1994;74:369-76 pubmed
    ..These observations indicate that HCO3-influx via an anion exchanger may be involved in the signal transduction pathway of U-46619 in rat platelets. ..
  21. Kolh P, Rolin S, Tchana Sato V, Petein M, Ghuysen A, Lambermont B, et al. Evaluation of BM-573, a novel TXA2 synthase inhibitor and receptor antagonist, in a porcine model of myocardial ischemia-reperfusion. Prostaglandins Other Lipid Mediat. 2006;79:53-73 pubmed
    ..These data suggest that BM-573 failed to prevent reperfusion injury in acutely ischemic pigs. ..
  22. Gao H, Welch W, DiBona G, Wilcox C. Sympathetic nervous system and hypertension during prolonged TxA2/PGH2 receptor activation in rats. Am J Physiol. 1997;273:H734-9 pubmed
  23. Romstedt K, Shin Y, Shams G, Doyle K, Tantishaiyakul V, Clark M, et al. Halogen-substituted trimetoquinol analogs as thromboxane A2 receptor antagonists in platelets and aorta. Biochem Pharmacol. 1993;46:2051-9 pubmed
  24. Crane G, Garland C. Thromboxane receptor stimulation associated with loss of SKCa activity and reduced EDHF responses in the rat isolated mesenteric artery. Br J Pharmacol. 2004;142:43-50 pubmed
    ..6. An early consequence of TXA(2) receptor stimulation is a reduction in the arterial hyperpolarization and relaxation attributed to EDHF. This effect appears to reflect a loss of SK(Ca) activity. ..
  25. Williams S, Dorn G, Rapoport R. Prostaglandin I2 mediates contraction and relaxation of vascular smooth muscle. Am J Physiol. 1994;267:H796-803 pubmed
    ..0 and 2.3 microM, respectively. These results suggest that 1) PGI2 induces relaxation through a PGI2-PGE1 receptor, and 2) higher concentrations of PGI2 act at the TxA2-PGH2 receptor to decrease PGI2-induced relaxation. ..
  26. Valentin F, Tippins J, Field M. The role of alternative splicing and C-terminal amino acids in thromboxane receptor stabilization. Biochem Biophys Res Commun. 2005;329:898-904 pubmed
    ..These data identify a region of the thromboxane receptor that is responsible for responding to oxidative challenge and open the possibility of identification of the molecular machinery underpinning this response. ..
  27. Hennenberg M, Tamalunas A, Wang Y, Keller P, Schott M, Strittmatter F, et al. Inhibition of agonist-induced smooth muscle contraction by picotamide in the male human lower urinary tract outflow region. Eur J Pharmacol. 2017;803:39-47 pubmed publisher
    ..This distinguishes picotamide from current medical treatments for LUTS, and suggests that picotamide may induce urodynamic effects in vivo. ..
  28. Andoh T, Maki T, Li S, Uta D. β2-Microglobulin elicits itch-related responses in mice through the direct activation of primary afferent neurons expressing transient receptor potential vanilloid 1. Eur J Pharmacol. 2017;810:134-140 pubmed publisher
    ..These results suggest that β2-MG is a pruritogen and elicits itch-related responses, at least in part, through TRPV1-expressing primary sensory neurons. ..
  29. Yang D, Feletou M, Levens N, Zhang J, Vanhoutte P. A diffusible substance(s) mediates endothelium-dependent contractions in the aorta of SHR. Hypertension. 2003;41:143-8 pubmed
    ..The production of this contracting factor(s) requires the activation of endothelial cyclooxygenase-1, and its action the activation of TP receptors on the vascular smooth muscle cells. ..
  30. Jeremy J, Mikhailidis D. U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade. Cardiovasc Res. 2002;54:701 pubmed
  31. Golino P, Ambrosio G, Villari B, Ragni M, Focaccio A, Pace L, et al. Endogenous prostaglandin endoperoxides may alter infarct size in the presence of thromboxane synthase inhibition: studies in a rabbit model of coronary artery occlusion-reperfusion. J Am Coll Cardiol. 1993;21:493-501 pubmed
    ..The simultaneous inhibition of thromboxane A2 synthase and blockade of thromboxane A2/PGH2 receptors by R 68070 identify a pharmacologic interaction of potential therapeutic importance. ..
  32. Martinson E, Scheible S, Marx Grunwitz A, Presek P. Secreted ADP plays a central role in thrombin-induced phospholipase D activation in human platelets. Thromb Haemost. 1998;80:976-81 pubmed
    ..Based on these findings, we conclude that ADP secretion and activation of purinergic ADP receptors is an important amplification mechanism in the signal transduction pathways leading to PLD activation in human platelets. ..
  33. Bowling N, Dube G, Kurtz W, Brune K, Saussy D, Dorn G, et al. Characterization of thromboxane A2/prostaglandin H2 binding sites in guinea pig cardiac membrane preparations. J Mol Cell Cardiol. 1994;26:915-23 pubmed
    ..125I]IBOP binding to GPA and GPV was completely displaced by the TXA2/PGH2 agonist U46619 and by the TXA2/PGH2 antagonist SQ29548.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  34. Pfister S, Pratt P, Kurian J, Campbell W. Glibenclamide inhibits thromboxane-mediated vasoconstriction by thromboxane receptor blockade. Vascul Pharmacol. 2004;40:285-92 pubmed
    ..These studies provide the first evidence that the ability of glibenclamide to inhibit TX-mediated contractions occurs independent of the vascular K(ATP) channel and is, instead, mediated by the blockade of the vascular TX receptor. ..
  35. Chua C, Hamdy R, Chua B. Regulation of endothelin-1 production by a thromboxane A2 mimetic in rat heart smooth muscle cells. Biochim Biophys Acta. 1996;1313:1-5 pubmed
    ..These results show that the short-lived TXA2 can induce potent and long-lived ET-1. These findings support a potential role for ET-1 in the pathogenesis of coronary atherosclerosis and hypertension evoked by TXA2. ..
  36. Wikström Jonsson E, Rosenqvist U, Dahlen S. Agonist and antagonist activities of the leukotriene analogue BAY u9773 in guinea pig lung parenchyma. Eur J Pharmacol. 1998;357:203-11 pubmed
  37. Denniss S, Ford R, Smith C, Jeffery A, Rush J. Chronic in vivo or acute in vitro resveratrol attenuates endothelium-dependent cyclooxygenase-mediated contractile signaling in hypertensive rat carotid artery. J Appl Physiol (1985). 2016;120:1141-50 pubmed publisher
  38. Tang E, Vanhoutte P. Endothelial dysfunction: a strategic target in the treatment of hypertension?. Pflugers Arch. 2010;459:995-1004 pubmed publisher
    ..Thus, endothelial dysfunction needs to be considered as a strategic target in the treatment of hypertension. ..
  39. Daray F, Minvielle A, Puppo S, Rothlin R. Pharmacological characterization of prostanoid receptors mediating vasoconstriction in human umbilical vein. Br J Pharmacol. 2003;139:1409-16 pubmed
    ..On the other hand, the results employing FP receptor agonists and antagonists of different prostanoid receptors suggest the presence of FP receptors mediating vasoconstriction in this vessel. ..
  40. Baldassare J, Tarver A, Henderson P, Mackin W, Sahagan B, Fisher G. Reconstitution of thromboxane A2 receptor-stimulated phosphoinositide hydrolysis in isolated platelet membranes: involvement of phosphoinositide-specific phospholipase C-beta and GTP-binding protein Gq. Biochem J. 1993;291 ( Pt 1):235-40 pubmed
    ..These results show the functional specificity of GTP-binding proteins and phospholipase C isoenzymes in mediating agonist-induced phosphoinositide hydrolysis in human platelets. ..
  41. Sebekova K, Ramuscak A, Boor P, Heidland A, Amann K. The selective TP receptor antagonist, S18886 (terutroban), attenuates renal damage in the double transgenic rat model of hypertension. Am J Nephrol. 2008;28:47-53 pubmed
    b>Thromboxane receptors play a decisive role in the renovascular actions of angiotensin II...
  42. Spurney R. Regulation of thromboxane receptor (TP) phosphorylation by protein phosphatase 1 (PP1) and PP2A. J Pharmacol Exp Ther. 2001;296:592-9 pubmed
    ..These data suggest that PP1- and PP2A-like protein phosphatases dephosphorylate TP. By regulating the phosphorylation state of TP, protein phosphatases may modulate tissue responsiveness to thromboxane. ..
  43. Wan Z, Woodward D, Cornell C, Fliri H, Martos J, Pettit S, et al. Bimatoprost, prostamide activity, and conventional drainage. Invest Ophthalmol Vis Sci. 2007;48:4107-15 pubmed
    ..The findings indicate that bimatoprost interacts with a prostamide receptor in the trabecular meshwork to increase outflow facility. ..
  44. Arakida Y, Ohga K, Kobayashi S, Yokota M, Miyata K, Yamada T, et al. Binding of YM158, a new dual antagonist for leukotriene D4 and thromboxane A2 receptors, to guinea pig lung membranes. Eur J Pharmacol. 1998;362:229-33 pubmed
    ..These studies indicate that YM158 is a highly selective dual antagonist for leukotriene D4 and thromboxane A2 receptors, and this has potential clinical and research applications. ..
  45. Kitamura N, Hukuda R, Majima T, Horie T, Sugihara T. [The 3 effective cases of cough variant asthma with ramatroban]. Arerugi. 2003;52:1089-92 pubmed
  46. Jin B, Hopfinger A. A proposed common spatial pharmacophore and the corresponding active conformations of some TxA2 receptor antagonists. J Chem Inf Comput Sci. 1994;34:1014-21 pubmed
    ..A unique spatial pharmacophore was identified and may be a useful template in designing a new TxA2 antagonists. ..
  47. Hsu K, Huang C, Kan W, Gean P. TXA2 agonists inhibit high-voltage-activated calcium channels in rat hippocampal CA1 neurons. Am J Physiol. 1996;271:C1269-77 pubmed
  48. Bowen I, Marr C, Chester A, Wheeler Jones C, Elliott J. In-vitro contraction of the equine aortic valve. J Heart Valve Dis. 2004;13:593-9 pubmed
    ..In this respect, the horse should be considered as a model of the human condition. ..
  49. Amano H, Nakamura M, Ito Y, Kakutani H, Eshima K, Kitasato H, et al. Thromboxane A synthase enhances blood flow recovery from hindlimb ischemia. J Surg Res. 2016;204:153-63 pubmed publisher
    ..These results indicated that local administration of C57-mTXAS-induced angiogenesis by activated platelets that bind to PSGL-1 on ischemic endothelial cells. ..
  50. Xiang L, Naik J, Abram S, Hester R. Chronic hyperglycemia impairs functional vasodilation via increasing thromboxane-receptor-mediated vasoconstriction. Am J Physiol Heart Circ Physiol. 2007;292:H231-6 pubmed
    ..These results suggest that the impaired functional vasodilation in diabetic rats is due to hyperglycemia-mediated increases in TP-mediated vasoconstriction. ..
  51. Yasui K, Asanuma F, Arimura A. Inhibitory effect of a TP-receptor antagonist, S-1452, on antigen-induced nasal plasma exudation in guinea pig model for allergic rhinitis. Pharmacology. 2001;63:65-70 pubmed
    ..These results indicate that TxA(2) as well as histamine may play an important role in antigen-induced nasal plasma exudation in guinea pigs, and S-1452 can be expected to be useful for the treatment of allergic rhinitis. ..
  52. Wilcox C, Welch W. Thromboxane synthase and TP receptor mRNA in rat kidney and brain: effects of salt intake and ANG II. Am J Physiol Renal Physiol. 2003;284:F525-31 pubmed
    ..Thus TP-Rs are strongly dependent on ANG II acting on AT(1)-Rs, whereas TxA(2)-S is regulated differentially in the kidney cortex and brain stem by salt intake. ..
  53. Shimizu T, Yokotani K. Brain cyclooxygenase and prostanoid TP receptors are involved in centrally administered epibatidine-induced secretion of noradrenaline and adrenaline from the adrenal medulla in rats. Eur J Pharmacol. 2009;606:77-83 pubmed publisher