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Gene Review

Ptger2  -  prostaglandin E receptor 2 (subtype EP2)

Mus musculus

Synonyms: EP2, EP2 receptor, PGE receptor EP2 subtype, PGE2 receptor EP2 subtype, Prostaglandin E2 receptor EP2 subtype, ...
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Disease relevance of Ptger2


High impact information on Ptger2

  • To evaluate the physiologic role of the PGE2 EP2 receptor subtype, we created mice with targeted disruption of this gene (EP2-/-) [4].
  • When fed a diet high in salt, the EP2-/- mice developed profound systolic hypertension, whereas wild-type mice showed no change in systolic blood pressure [4].
  • EP2-/- mice develop normally but produce small litters and have slightly elevated baseline systolic blood pressure [4].
  • Analysis of wild-type and EP2-/- mice on day 5 of pregnancy indicated that the reduced litter size of EP2-/- mice is due to a pre-implantation defect [4].
  • However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4 [5].

Chemical compound and disease context of Ptger2

  • We previously cloned a cDNA for a mouse PGE receptor positively coupled to adenylate cyclase from mouse mastocytoma cells, and reported it as EP2 subtype of PGE receptor [Honda, A., Sugimoto, Y., Namba, T., Watabe, A., Irie, A., Negishi, M., Narumiya, S. and Ichikawa, A. (1993) J. Biol. Chem. 268, 7759-7762] [6].
  • Prostaglandin estradiol (PGE(2)) stimulates bone resorption by a cyclic AMP (cAMP)-dependent mechanism that involves prostaglandin E receptors of the EP2 and EP4 subtypes [7].
  • Misoprostol, which is selective for both EP2- and EP3-receptors, inhibited the edema response to ZAS (> 40%) but had no effect on the response to PAF [8].
  • Spinal prostaglandin E receptors of the EP2 subtype and the glycine receptor alpha3 subunit, which mediate central inflammatory hyperalgesia, do not contribute to pain after peripheral nerve injury or formalin injection [9].

Biological context of Ptger2


Anatomical context of Ptger2


Associations of Ptger2 with chemical compounds


Regulatory relationships of Ptger2


Other interactions of Ptger2

  • PGE(2) can modulate inflammatory reactions via the EP2/4 receptor through its regulation of TNF-alpha and IL-6 [20].
  • In conclusion, our data indicate that LPS activates airway epithelial TLR4 to cause release of PGE(2) and subsequent EP2 and EP4 receptor-dependent smooth muscle relaxation [23].
  • Tbxa2r mapped to Chr 10, Ptgerep2 mapped to the distal end of Chr 3 [24].
  • M&B-28767, a putative EP3 agonist, and misoprostol, a putative EP2/EP3 agonist, also bound to this receptor with Ki values of 120 nM [25].
  • Interestingly, PGE2 utilized the same EP2 receptor-mediated signal transduction mechanism to down-regulate the expression of the inducible NO synthase and the production of NO [26].

Analytical, diagnostic and therapeutic context of Ptger2


  1. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Sonoshita, M., Takaku, K., Sasaki, N., Sugimoto, Y., Ushikubi, F., Narumiya, S., Oshima, M., Taketo, M.M. Nat. Med. (2001) [Pubmed]
  2. The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia. Chang, S.H., Ai, Y., Breyer, R.M., Lane, T.F., Hla, T. Cancer Res. (2005) [Pubmed]
  3. Neuroprotective function of the PGE2 EP2 receptor in cerebral ischemia. McCullough, L., Wu, L., Haughey, N., Liang, X., Hand, T., Wang, Q., Breyer, R.M., Andreasson, K. J. Neurosci. (2004) [Pubmed]
  4. Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. Kennedy, C.R., Zhang, Y., Brandon, S., Guan, Y., Coffee, K., Funk, C.D., Magnuson, M.A., Oates, J.A., Breyer, M.D., Breyer, R.M. Nat. Med. (1999) [Pubmed]
  5. Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis. Honda, T., Segi-Nishida, E., Miyachi, Y., Narumiya, S. J. Exp. Med. (2006) [Pubmed]
  6. Identification of prostaglandin E receptor 'EP2' cloned from mastocytoma cells EP4 subtype. Nishigaki, N., Negishi, M., Honda, A., Sugimoto, Y., Namba, T., Narumiya, S., Ichikawa, A. FEBS Lett. (1995) [Pubmed]
  7. Effects of selective prostaglandin EP4 receptor antagonist on osteoclast formation and bone resorption in vitro. Tomita, M., Li, X., Okada, Y., Woodiel, F.N., Young, R.N., Pilbeam, C.C., Raisz, L.G. Bone (2002) [Pubmed]
  8. Anti-inflammatory effect of prostanoids in mouse and rat skin: evidence for a role of EP3-receptors. Ahluwalia, A., Perretti, M. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  9. Spinal prostaglandin E receptors of the EP2 subtype and the glycine receptor alpha3 subunit, which mediate central inflammatory hyperalgesia, do not contribute to pain after peripheral nerve injury or formalin injection. H??sl, K., Reinold, H., Harvey, R.J., M??ller, U., Narumiya, S., Zeilhofer, H.U. Pain (2006) [Pubmed]
  10. Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. Elvin, J.A., Yan, C., Matzuk, M.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  11. Stimulation of Prostaglandin EP2 Receptors Prevents NMDA-Induced Excitotoxicity. Ahmad, A.S., Zhuang, H., Echeverria, V., Dor??, S. J. Neurotrauma (2006) [Pubmed]
  12. Prostaglandin E2 receptors of the EP2 and EP4 subtypes regulate activation and differentiation of mouse B lymphocytes to IgE-secreting cells. Fedyk, E.R., Phipps, R.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  13. Lack of expression of the EP2 but not EP3 receptor for prostaglandin E2 results in suppression of skin tumor development. Sung, Y.M., He, G., Fischer, S.M. Cancer Res. (2005) [Pubmed]
  14. Prostaglandin E2 stimulates granulocyte colony-stimulating factor production via the prostanoid EP2 receptor in mouse peritoneal neutrophils. Sugimoto, Y., Fukada, Y., Mori, D., Tanaka, S., Yamane, H., Okuno, Y., Deai, K., Tsuchiya, S., Tsujimoto, G., Ichikawa, A. J. Immunol. (2005) [Pubmed]
  15. Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. Nataraj, C., Thomas, D.W., Tilley, S.L., Nguyen, M.T., Mannon, R., Koller, B.H., Coffman, T.M. J. Clin. Invest. (2001) [Pubmed]
  16. Biphasic effect of prostaglandin E2 on osteoclast formation in spleen cell cultures: role of the EP2 receptor. Ono, K., Kaneko, H., Choudhary, S., Pilbeam, C.C., Lorenzo, J.A., Akatsu, T., Kugai, N., Raisz, L.G. J. Bone Miner. Res. (2005) [Pubmed]
  17. Peptidoglycan-induced IL-6 production in RAW 264.7 macrophages is mediated by cyclooxygenase-2, PGE2/PGE4 receptors, protein kinase A, I kappa B kinase, and NF-kappa B. Chen, B.C., Liao, C.C., Hsu, M.J., Liao, Y.T., Lin, C.C., Sheu, J.R., Lin, C.H. J. Immunol. (2006) [Pubmed]
  18. Characterization of prostanoid receptors in podocytes. Bek, M., Nüsing, R., Kowark, P., Henger, A., Mundel, P., Pavenstädt, H. J. Am. Soc. Nephrol. (1999) [Pubmed]
  19. Sequential down-regulation of E-cadherin with squamous cell carcinoma progression: loss of E-cadherin via a prostaglandin E2-EP2 dependent posttranslational mechanism. Brouxhon, S., Kyrkanides, S., O'Banion, M.K., Johnson, R., Pearce, D.A., Centola, G.M., Miller, J.N., McGrath, K.H., Erdle, B., Scott, G., Schneider, S., VanBuskirk, J., Pentland, A.P. Cancer Res. (2007) [Pubmed]
  20. Prostaglandin E2 receptors EP2 and EP4 are up-regulated in peritoneal macrophages and joints of pristane-treated mice and modulate TNF-alpha and IL-6 production. Akaogi, J., Yamada, H., Kuroda, Y., Nacionales, D.C., Reeves, W.H., Satoh, M. J. Leukoc. Biol. (2004) [Pubmed]
  21. Knockout of the murine prostaglandin EP2 receptor impairs osteoclastogenesis in vitro. Li, X., Okada, Y., Pilbeam, C.C., Lorenzo, J.A., Kennedy, C.R., Breyer, R.M., Raisz, L.G. Endocrinology (2000) [Pubmed]
  22. Microglia lacking E Prostanoid Receptor subtype 2 have enhanced Abeta phagocytosis yet lack Abeta-activated neurotoxicity. Shie, F.S., Breyer, R.M., Montine, T.J. Am. J. Pathol. (2005) [Pubmed]
  23. Lipopolysaccharide Induces Epithelium- and Prostaglandin E2-Dependent Relaxation of Mouse Isolated Trachea through Activation of Cyclooxygenase (COX)-1 and COX-2. Balzary, R.W., Cocks, T.M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  24. 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]
  25. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Kiriyama, M., Ushikubi, F., Kobayashi, T., Hirata, M., Sugimoto, Y., Narumiya, S. Br. J. Pharmacol. (1997) [Pubmed]
  26. Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions. Levi, G., Minghetti, L., Aloisi, F. Biochimie (1998) [Pubmed]
  27. The mouse prostaglandin E receptor EP2 subtype: cloning, expression, and northern blot analysis. Katsuyama, M., Nishigaki, N., Sugimoto, Y., Morimoto, K., Negishi, M., Narumiya, S., Ichikawa, A. FEBS Lett. (1995) [Pubmed]
  28. The effect of deletion of cyclooxygenase-2, prostaglandin receptor EP2, or EP4 in bone marrow cells on osteoclasts induced by mouse mammary cancer cell lines. Ono, K., Akatsu, T., Kugai, N., Pilbeam, C.C., Raisz, L.G. Bone (2003) [Pubmed]
  29. Expression of messenger RNA for prostaglandin E receptor subtypes EP4/EP2 and cyclooxygenase isozymes in mouse periovulatory follicles and oviducts during superovulation. Segi, E., Haraguchi, K., Sugimoto, Y., Tsuji, M., Tsunekawa, H., Tamba, S., Tsuboi, K., Tanaka, S., Ichikawa, A. Biol. Reprod. (2003) [Pubmed]
  30. Embryonic stem cell lines from MRL mice allow genetic modification in a murine model of autoimmune disease. Goulet, J.L., Wang, C.Y., Koller, B.H. J. Immunol. (1997) [Pubmed]
  31. PGE2 signal through EP2 promotes the growth of articular chondrocytes. Aoyama, T., Liang, B., Okamoto, T., Matsusaki, T., Nishijo, K., Ishibe, T., Yasura, K., Nagayama, S., Nakayama, T., Nakamura, T., Toguchida, J. J. Bone Miner. Res. (2005) [Pubmed]
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