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Gene Review

Ptger3  -  prostaglandin E receptor 3 (subtype EP3)

Mus musculus

Synonyms: EP3, PGE receptor EP3 subtype, PGE2 receptor EP3 subtype, Pgerep3, Prostaglandin E2 receptor EP3 subtype, ...
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Disease relevance of Ptger3

  • Further, implanted tumor growth (sarcoma-180, Lewis lung carcinoma) was markedly suppressed in EP3(-/-), in which tumor-associated angiogenesis was also reduced [1].
  • EP3 antagonism had no effect on tumor metastasis [2].
  • The augmentation of EP3-mediated cAMP synthesis was dose-dependent, without affecting the half-maximal concentration for EP4-mediated G(s)-activity, which was inhibited by a G(i) inhibitor, pertussis toxin [3].
  • Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4 [3].
  • Addition of an inhibitor of protein kinase A, H89, or an inhibitor of MMPs, BB94, significantly suppressed bone-resorbing activity induced by PGE(2.) In calvarial culture from EP1-, EP2-, and EP3-knockout mice, PGE(2) stimulated bone resorption to an extent similar to that found in calvaria from the wild-type mice [4].

Psychiatry related information on Ptger3


High impact information on Ptger3


Chemical compound and disease context of Ptger3


Biological context of Ptger3


Anatomical context of Ptger3

  • Similar expression patterns of EP3 and EP4 in the Day 4 pseudopregnant mouse uterus or in the ovariectomized uterus under combined treatment with estrogen and progesterone suggest that these genes are regulated by ovarian steroids rather than by the embryo during the preimplantation period (Days 1-4) [17].
  • The results suggest the important roles of COX-2 induction and the PGE2-EP3 receptor system in the dorsal root ganglia in the development but not maintenance of acute herpetic pain [18].
  • Expression of EP3 and FP primarily in the circular muscle of the myometrium on Days 3-5 of pregnancy suggests that the circular muscle, not the longitudinal muscle, is the primary target for PG-mediated uterine contractions required for embryo transport, spacing, and/or accommodation in the uterus [17].
  • In conclusion, these findings suggest that PGE(2) accelerates RGD-dependent adhesion via cooperative activation between EP3 and EP4 and contributes to the recruitment of mast cells to the ECM during inflammation [3].
  • Expression of EP1 in the liver and EP4 receptor in white adipose tissue were upregulated and responded to indomethacin treatment, while downregulated expression of EP3 in skeletal muscle from tumor-bearing mice was unresponsive to indomethacin treatment despite improved carcass weight [19].

Associations of Ptger3 with chemical compounds

  • We examined the development of aberrant crypt foci (ACFs), putative preneoplastic lesions of the colon, in two lines of knockout mice, each deficient in prostaglandin E receptors, EP1 and EP3, by treatment with the colon carcinogen, azoxymethane [20].
  • Furthermore, PGE(2), an EP2 agonist (butaprost), an EP2/PGE(3) (EP3)/EP4 agonist (misoprostol), and misoprostol in the presence of AH6809 all induced IL-6 production, whereas an EP1/EP3 agonist (sulprostone) did not [21].
  • Involvement of cyclooxygenase-2 and EP3 prostaglandin receptor in acute herpetic but not postherpetic pain in mice [18].
  • PGE(2) increased gastric HCO(3)(-) secretion in both rats and WT mice, and this action was inhibited by ONO-8711 and disappeared in EP1 (-/-) but not EP3 (-/-) mice [22].
  • Furthermore, treatment with piroxicam results in significantly lower [Ca(2+)](i) in tumors, and this effect is attenuated by concomitant treatment with the EP1/EP3 receptor agonist 17-phenyl-trinor-PGE(2) [23].

Physical interactions of Ptger3


Regulatory relationships of Ptger3

  • RT-PCR revealed that EP1, EP2, and EP3 were expressed in rat calvariae and that osteoblastic cells (MC3T3-E1) expressed EP1 and EP2 [25].
  • PGE2 worked as a mediator of febrile responses to both endogenous and exogenous pyrogens and as a regulator of bicarbonate secretion induced by acid-stimulation in the duodenum via the EP3 [26].
  • Rat hepatocytes have previously been reported to possess prostaglandin E2 receptors of the EP3-type (EP3-receptors) that inhibit glucagon-stimulated glycogenolysis by decreasing cAMP [27].

Other interactions of Ptger3

  • Mapping of the genes encoding mouse thromboxane A2 receptor and prostaglandin E receptor subtypes EP2 and EP3 [28].
  • Unlike EP3 knockout mice, the EP2 knockout mice produced significantly fewer tumors and reduced tumor incidence compared with wild type (WT) mice in a 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) two-stage carcinogenesis protocol [29].
  • The mRNA for EP3 subtype, which is coupled to inhibition of adenylate cyclase, was located densely in the tubules in the outer medulla and in the distal tubules in the cortex [30].
  • Butaprost (EP2 agonist) but not sulprostone (EP3 agonist) inhibited IL-6-stimulated proliferation [31].
  • CGRP level during ethanol perfusion was not increased in IP(-/-) but was increased in EP3(-/-) and wild-type counterparts after preperfusion of 1 mol/L NaCl [32].

Analytical, diagnostic and therapeutic context of Ptger3


  1. Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. Amano, H., Hayashi, I., Endo, H., Kitasato, H., Yamashina, S., Maruyama, T., Kobayashi, M., Satoh, K., Narita, M., Sugimoto, Y., Murata, T., Yoshimura, H., Narumiya, S., Majima, M. J. Exp. Med. (2003) [Pubmed]
  2. Prostaglandin E receptor EP4 antagonism inhibits breast cancer metastasis. Ma, X., Kundu, N., Rifat, S., Walser, T., Fulton, A.M. Cancer Res. (2006) [Pubmed]
  3. Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4. Hatae, N., Kita, A., Tanaka, S., Sugimoto, Y., Ichikawa, A. J. Biol. Chem. (2003) [Pubmed]
  4. Impaired bone resorption to prostaglandin E2 in prostaglandin E receptor EP4-knockout mice. Miyaura, C., Inada, M., Suzawa, T., Sugimoto, Y., Ushikubi, F., Ichikawa, A., Narumiya, S., Suda, T. J. Biol. Chem. (2000) [Pubmed]
  5. Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors. Oka, T., Oka, K., Kobayashi, T., Sugimoto, Y., Ichikawa, A., Ushikubi, F., Narumiya, S., Saper, C.B. J. Physiol. (Lond.) (2003) [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. Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3. Kunikata, T., Yamane, H., Segi, E., Matsuoka, T., Sugimoto, Y., Tanaka, S., Tanaka, H., Nagai, H., Ichikawa, A., Narumiya, S. Nat. Immunol. (2005) [Pubmed]
  8. 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]
  9. Anorexia and cachexia in prostaglandin EP1 and EP3 subtype receptor knockout mice bearing a tumor with high intrinsic PGE2 production and prostaglandin related cachexia. Wang, W., Andersson, M., Lönnroth, C., Svanberg, E., Lundholm, K. J. Exp. Clin. Cancer Res. (2005) [Pubmed]
  10. 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]
  11. Characterization of the prostaglandin E receptor expressed on a cultured mast cell line, BNu-2cl3. Nishigaki, N., Negishi, M., Sugimoto, Y., Namba, T., Narumiya, S., Ichikawa, A. Biochem. Pharmacol. (1993) [Pubmed]
  12. Characterization of EP receptor subtypes responsible for prostaglandin E2-induced pain responses by use of EP1 and EP3 receptor knockout mice. Minami, T., Nakano, H., Kobayashi, T., Sugimoto, Y., Ushikubi, F., Ichikawa, A., Narumiya, S., Ito, S. Br. J. Pharmacol. (2001) [Pubmed]
  13. Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation. Fabre, J.E., Nguyen, M., Athirakul, K., Coggins, K., McNeish, J.D., Austin, S., Parise, L.K., FitzGerald, G.A., Coffman, T.M., Koller, B.H. J. Clin. Invest. (2001) [Pubmed]
  14. Cloning and expression of a cDNA for mouse prostaglandin E receptor EP2 subtype. Honda, A., Sugimoto, Y., Namba, T., Watabe, A., Irie, A., Negishi, M., Narumiya, S., Ichikawa, A. J. Biol. Chem. (1993) [Pubmed]
  15. A cluster of aromatic amino acids in the i2 loop plays a key role for Gs coupling in prostaglandin EP2 and EP3 receptors. Sugimoto, Y., Nakato, T., Kita, A., Takahashi, Y., Hatae, N., Tabata, H., Tanaka, S., Ichikawa, A. J. Biol. Chem. (2004) [Pubmed]
  16. Downregulation of prostaglandin E receptor subtype EP3 during colon cancer development. Shoji, Y., Takahashi, M., Kitamura, T., Watanabe, K., Kawamori, T., Maruyama, T., Sugimoto, Y., Negishi, M., Narumiya, S., Sugimura, T., Wakabayashi, K. Gut (2004) [Pubmed]
  17. Potential sites of prostaglandin actions in the periimplantation mouse uterus: differential expression and regulation of prostaglandin receptor genes. Yang, Z.M., Das, S.K., Wang, J., Sugimoto, Y., Ichikawa, A., Dey, S.K. Biol. Reprod. (1997) [Pubmed]
  18. Involvement of cyclooxygenase-2 and EP3 prostaglandin receptor in acute herpetic but not postherpetic pain in mice. Takasaki, I., Nojima, H., Shiraki, K., Sugimoto, Y., Ichikawa, A., Ushikubi, F., Narumiya, S., Kuraishi, Y. Neuropharmacology (2005) [Pubmed]
  19. Prostaglandin E and prostacyclin receptor expression in tumor and host tissues from MCG 101-bearing mice: a model with prostanoid-related cachexia. Wang, W., Andersson, M., Lõnnroth, C., Svanberg, E., Lundholm, K. Int. J. Cancer (2005) [Pubmed]
  20. Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Watanabe, K., Kawamori, T., Nakatsugi, S., Ohta, T., Ohuchida, S., Yamamoto, H., Maruyama, T., Kondo, K., Ushikubi, F., Narumiya, S., Sugimura, T., Wakabayashi, K. Cancer Res. (1999) [Pubmed]
  21. 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]
  22. Involvement of cyclooxygenase-1, prostaglandin E2 and EP1 receptors in acid-induced HCO3- secretion in stomach. Takeuchi, K., Aihara, E., Sasaki, Y., Nomura, Y., Ise, F. J. Physiol. Pharmacol. (2006) [Pubmed]
  23. Prostaglandin E(2) protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in Apc(Min/+) mice. Hansen-Petrik, M.B., McEntee, M.F., Jull, B., Shi, H., Zemel, M.B., Whelan, J. Cancer Res. (2002) [Pubmed]
  24. Functional domains essential for Gs activity in prostaglandin EP2 and EP3 receptors. Sugimoto, Y., Nakato, T., Kita, A., Hatae, N., Tabata, H., Tanaka, S., Ichikawa, A. Life Sci. (2003) [Pubmed]
  25. Expression of prostaglandin E receptor subtypes in bone: expression of EP2 in bone development. Kasugai, S., Oida, S., Iimura, T., Arai, N., Takeda, K., Ohya, K., Sasaki, S. Bone (1995) [Pubmed]
  26. Roles of prostanoids revealed from studies using mice lacking specific prostanoid receptors. Ushikubi, F., Sugimoto, Y., Ichikawa, A., Narumiya, S. Jpn. J. Pharmacol. (2000) [Pubmed]
  27. Molecular cloning and expression of a prostaglandin E2 receptor of the EP3 beta subtype from rat hepatocytes. Neuschäfer-Rube, F., DeVries, C., Hänecke, K., Jungermann, K., Püschel, G.P. FEBS Lett. (1994) [Pubmed]
  28. 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]
  29. 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]
  30. Distinct cellular localization of mRNAs for three subtypes of prostaglandin E receptor in kidney. Sugimoto, Y., Namba, T., Shigemoto, R., Negishi, M., Ichikawa, A., Narumiya, S. Am. J. Physiol. (1994) [Pubmed]
  31. Prostaglandin E2 mediates growth arrest in NFS-60 cells by down-regulating interleukin-6 receptor expression. de Silva, K.I., Daud, A.N., Deng, J., Jones, S.B., Gamelli, R.L., Shankar, R. Biochem. J. (2003) [Pubmed]
  32. Adaptive cytoprotection mediated by prostaglandin I(2) is attributable to sensitization of CRGP-containing sensory nerves. Boku, K., Ohno, T., Saeki, T., Hayashi, H., Hayashi, I., Katori, M., Murata, T., Narumiya, S., Saigenji, K., Majima, M. Gastroenterology (2001) [Pubmed]
  33. Urinary concentrating function in mice lacking EP3 receptors for prostaglandin E2. Fleming, E.F., Athirakul, K., Oliverio, M.I., Key, M., Goulet, J., Koller, B.H., Coffman, T.M. Am. J. Physiol. (1998) [Pubmed]
  34. Prostaglandin E receptor subtypes in mouse osteoblastic cell line. Suda, M., Tanaka, K., Natsui, K., Usui, T., Tanaka, I., Fukushima, M., Shigeno, C., Konishi, J., Narumiya, S., Ichikawa, A., Nakao, N. Endocrinology (1996) [Pubmed]
  35. Expression and site-directed mutagenesis of mouse prostaglandin E2 receptor EP3 subtype in insect cells. Huang, C., Tai, H.H. Biochem. J. (1995) [Pubmed]
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