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Gene Review

Tbxa2r  -  thromboxane A2 receptor

Mus musculus

Synonyms: Prostanoid TP receptor, TP, TXA2-R, Thromboxane A2 receptor, Tp receptor
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Disease relevance of Tbxa2r

  • TP ligands, including COX-1 (but not COX-2)-derived TxA2, promote initiation and early progression of atherogenesis in Apobec-1/LDLR DKOs but appear unimportant in the maintenance of established disease [1].
  • Despite a marked effect on disease progression, TP antagonism failed to induce regression of established atherosclerotic disease in this model [1].
  • Thus, on the C57BL/6 background, TP receptors contribute to cardiac hypertrophy but not proteinuria [2].
  • Chronic angiotensin II infusion caused albuminuria only in the C57BL/6 strain, and TP deficiency did not alter its development [2].
  • In vivo, immune responses to foreign antigens are enhanced in TP-deficient mice, which also develop marked lymphadenopathy with age [3].

High impact information on Tbxa2r

  • The cytokine-induced increase in beating rate was markedly inhibited in atria from mice lacking either TP or FP receptors [4].
  • Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation [5].
  • Cell surface receptors for prostanoids have been characterized pharmacologically and the complementary DNAs for thromboxane A2 receptor and the EP3 subtype of the prostaglandin (PG)E receptor reveal that they belong to the seven-transmembrane-domain receptor family [6].
  • Here we show that DCs produce thromboxane A2 (TXA2), whereas naive T cells express the thromboxane receptor (TP) [3].
  • Thus, TXA2-TP signaling modulates acquired immunity by negatively regulating DC-T cell interactions [3].

Chemical compound and disease context of Tbxa2r


Biological context of Tbxa2r


Anatomical context of Tbxa2r

  • To investigate the mechanism responsible for reduced atherosclerosis in apoE(-/-)TP(-/-) mice, we examined the role of TP in bone marrow (BM)-derived cells in the development of the atherosclerotic lesions [14].
  • Endothelial cells genetically lacking TP show reduced inflammatory responses when stimulated with this product of lipid oxidation but not other oxidized lipids [7].
  • A TP agonist, 9,11-dideoxy-9alpha,11alpha-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U46619), enhanced IL-6 production in both 1321N1 cells and cultured mouse astrocytes [15].
  • In the airways, it has been postulated that TXA2 causes airway constriction by direct activation of thromboxane prostanoid (TP) receptors on airway smooth muscle cells [16].
  • Ribonuclease protection assays showed expression of TP RNA in several organs including thymus, spleen, kidney, and lung [17].

Associations of Tbxa2r with chemical compounds

  • Mapping of the genes encoding mouse thromboxane A2 receptor and prostaglandin E receptor subtypes EP2 and EP3 [18].
  • To evaluate the role of thromboxane in hypertension and its complications, we studied mice with targeted disruption of the TXA2 receptor gene in an angiotensin-II-dependent model of hypertension [2].
  • During chronic angiotensin II infusion (1000 ng/kg per minute x 28 days by subcutaneous osmotic pump), TP deficiency prevented mortality in the C57BL/6 background but not in the BALB/c strain [2].
  • In our study, we tested the effect of a novel TxA(2) receptor (TP) antagonist and synthase inhibitor, BM-573, on atherosclerosis development and progression in LDL receptor deficient mice [19].
  • 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 [20].

Physical interactions of Tbxa2r

  • Its actions are mediated by G protein-coupled thromboxane-prostanoid (TP) receptors [13].

Other interactions of Tbxa2r


Analytical, diagnostic and therapeutic context of Tbxa2r


  1. Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism. Egan, K.M., Wang, M., Fries, S., Lucitt, M.B., Zukas, A.M., Puré, E., Lawson, J.A., FitzGerald, G.A. Circulation (2005) [Pubmed]
  2. Role for thromboxane receptors in angiotensin-II-induced hypertension. Francois, H., Athirakul, K., Mao, L., Rockman, H., Coffman, T.M. Hypertension (2004) [Pubmed]
  3. Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity. Kabashima, K., Murata, T., Tanaka, H., Matsuoka, T., Sakata, D., Yoshida, N., Katagiri, K., Kinashi, T., Tanaka, T., Miyasaka, M., Nagai, H., Ushikubi, F., Narumiya, S. Nat. Immunol. (2003) [Pubmed]
  4. Thromboxane A2 and prostaglandin F2alpha mediate inflammatory tachycardia. Takayama, K., Yuhki, K., Ono, K., Fujino, T., Hara, A., Yamada, T., Kuriyama, S., Karibe, H., Okada, Y., Takahata, O., Taniguchi, T., Iijima, T., Iwasaki, H., Narumiya, S., Ushikubi, F. Nat. Med. (2005) [Pubmed]
  5. Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation. Rocca, B., Loeb, A.L., Strauss, J.F., Vezza, R., Habib, A., Li, H., FitzGerald, G.A. Nat. Med. (2000) [Pubmed]
  6. Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Namba, T., Sugimoto, Y., Negishi, M., Irie, A., Ushikubi, F., Kakizuka, A., Ito, S., Ichikawa, A., Narumiya, S. Nature (1993) [Pubmed]
  7. Involvement of thromboxane receptor in the proatherogenic effect of isoprostane F2alpha-III: evidence from apolipoprotein E- and LDL receptor-deficient mice. Tang, M., Cyrus, T., Yao, Y., Vocun, L., Praticò, D. Circulation (2005) [Pubmed]
  8. Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo. Liu, J., Fitzgerald, M.E., Berndt, M.C., Jackson, C.W., Gartner, T.K. Blood (2006) [Pubmed]
  9. Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Daniel, T.O., Liu, H., Morrow, J.D., Crews, B.C., Marnett, L.J. Cancer Res. (1999) [Pubmed]
  10. Effect of OKY-046 and ONO-3708 on liver injury in mice. Nagai, H., Aoki, M., Shimazawa, T., Yakuo, I., Koda, A., Kasahara, M. Jpn. J. Pharmacol. (1989) [Pubmed]
  11. The effect of a thromboxane A2 receptor antagonist BAY-u-3405 on experimental allergic reactions. Nagai, H., Takeda, H., Yamaguchi, S., Tanaka, H., Matsuo, A., Inagaki, N. Prostaglandins (1995) [Pubmed]
  12. Thromboxane A2 receptor is highly expressed in mouse immature thymocytes and mediates DNA fragmentation and apoptosis. Ushikubi, F., Aiba, Y., Nakamura, K., Namba, T., Hirata, M., Mazda, O., Katsura, Y., Narumiya, S. J. Exp. Med. (1993) [Pubmed]
  13. Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2. Thomas, D.W., Mannon, R.B., Mannon, P.J., Latour, A., Oliver, J.A., Hoffman, M., Smithies, O., Koller, B.H., Coffman, T.M. J. Clin. Invest. (1998) [Pubmed]
  14. Protection of atherogenesis in thromboxane A2 receptor-deficient mice is not associated with thromboxane A2 receptor in bone marrow-derived cells. Zhuge, X., Arai, H., Xu, Y., Murayama, T., Kobayashi, T., Narumiya, S., Kita, T., Yokode, M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. Thromboxane A2 promotes interleukin-6 biosynthesis mediated by an activation of cyclic AMP-response element-binding protein in 1321N1 human astrocytoma cells. Obara, Y., Kurose, H., Nakahata, N. Mol. Pharmacol. (2005) [Pubmed]
  16. Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism. Allen, I.C., Hartney, J.M., Coffman, T.M., Penn, R.B., Wess, J., Koller, B.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  17. Structure and expression of the murine thromboxane A2 receptor gene. Båtshake, B., Nilsson, C., Sundelin, J. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  18. Mapping of the genes encoding mouse thromboxane A2 receptor and prostaglandin E receptor subtypes EP2 and EP3. Taketo, M., Rochelle, J.M., Sugimoto, Y., Namba, T., Honda, A., Negishi, M., Ichikawa, A., Narumiya, S., Seldin, M.F. Genomics (1994) [Pubmed]
  19. A novel thromboxane receptor antagonist and synthase inhibitor, BM-573, reduces development and progression of atherosclerosis in LDL receptor deficient mice. Cyrus, T., Yao, Y., Ding, T., Dogné, J.M., Praticò, D. Eur. J. Pharmacol. (2007) [Pubmed]
  20. 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]
  21. Cloning and expression of cDNA for a mouse EP1 subtype of prostaglandin E receptor. Watabe, A., Sugimoto, Y., Honda, A., Irie, A., Namba, T., Negishi, M., Ito, S., Narumiya, S., Ichikawa, A. J. Biol. Chem. (1993) [Pubmed]
  22. COX-2-dependent cardiac failure in Gh/tTG transgenic mice. Zhang, Z., Vezza, R., Plappert, T., McNamara, P., Lawson, J.A., Austin, S., Praticò, D., Sutton, M.S., FitzGerald, G.A. Circ. Res. (2003) [Pubmed]
  23. TP receptors regulate renal hemodynamics during angiotensin II slow pressor response. Kawada, N., Dennehy, K., Solis, G., Modlinger, P., Hamel, R., Kawada, J.T., Aslam, S., Moriyama, T., Imai, E., Welch, W.J., Wilcox, C.S. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  24. Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot analysis. Namba, T., Sugimoto, Y., Hirata, M., Hayashi, Y., Honda, A., Watabe, A., Negishi, M., Ichikawa, A., Narumiya, S. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  25. Mechanisms mediating the vasoactive effects of the B1 receptors of bradykinin. Duka, I., Duka, A., Kintsurashvili, E., Johns, C., Gavras, I., Gavras, H. Hypertension (2003) [Pubmed]
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