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Gene Review

Ptger1  -  prostaglandin E receptor 1 (subtype EP1)

Mus musculus

Synonyms: 42kDa, EP1, PGE receptor EP1 subtype, PGE2 receptor EP1 subtype, Prostaglandin E2 receptor EP1 subtype, ...
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Disease relevance of Ptger1


Psychiatry related information on Ptger1

  • Prostaglandin E receptor EP1 controls impulsive behavior under stress [5].
  • We now show that, under social or environmental stress, mice deficient in prostaglandin E receptor subtype EP1 (Ptger1(-/-)) manifest behavioral disinhibition, including impulsive aggression with defective social interaction, impaired cliff avoidance, and an exaggerated acoustic startle response [5].
  • Both EP1 and EP3 receptor KO mice showed a normal circadian cycle of Tc and brief hyperthermia following psychological stress (cage-exchange stress and buddy-removal stress) [6].

High impact information on Ptger1

  • We therefore sought to identify the downstream effectors of COX-2 neurotoxicity, and found that prostaglandin E(2) EP1 receptors are essential for the neurotoxicity mediated by COX-2-derived prostaglandin E(2) [4].
  • EP1 receptors disrupt Ca(2+) homeostasis by impairing Na(+)-Ca(2+) exchange, a key mechanism by which neurons cope with excess Ca(2+) accumulation after an excitotoxic insult [4].
  • Thus, EP1 receptors contribute to neurotoxicity by augmenting the Ca(2+) dysregulation underlying excitotoxic neuronal death [4].
  • The absence of either the EP1 or EP3 receptors did not alter the inhibitory response to PGE(2) in the MLR [7].
  • There are four receptors for PGE(2) (EP1-EP4) with unique patterns of expression and different coupling to intracellular signaling pathways [7].

Chemical compound and disease context of Ptger1

  • Saline-injected EP1(-/-) mice showed hyperalgesia, which was reversed by i.t. PGE2 in a dose-dependent manner [8].
  • Sulprostone, which is selective for EP1 and EP3 PGE-receptors, produced a potent inhibition of the edema responses to both ZAS (80%) and PAF (60%) [9].

Biological context of Ptger1


Anatomical context of Ptger1

  • These data indicate that in podocytes, PGE2 regulates distinct cellular functions via the EP1 and EP4 receptor, thereby increasing [Ca2+]i and cAMP, respectively [14].
  • Strong signals for EP1 transcripts were detected in cells of the muscularis mucosae layer, especially in the body of the stomach [15].
  • In addition, the HCO3- stimulatory action of sulprostone (EP1/EP3 agonist) in the stomach was inhibited by the Ca2+ antagonist verapamil but not affected by IBMX, the inhibitor of phosphodiesterase, while that in the duodenum was inhibited by verapamil and enhanced by IBMX [16].
  • Immunohistochemical analysis of EP receptor staining in unirradiated and UVB-exposed SKH-1 mouse skin demonstrated the localization of EP1 and EP2 to the plasma membrane of differentiated epidermal keratinocytes [17].
  • Analysis of c-Fos expression as a marker for neuronal activity indicated that both EP1 and EP3 contribute to activation of neurons in the paraventricular nucleus of the hypothalamus (PVN) [18].

Associations of Ptger1 with chemical compounds

  • These results strongly suggest that prostaglandin E2 contributes to colon carcinogenesis to some extent through its action at the EP1 receptor [2].
  • Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis [2].
  • Administration of 250, 500, or 1000 ppm of a novel selective EP1 antagonist, ONO-8711, in the diet to azoxymethane-treated C57BL/6J mice also resulted in a dose-dependent reduction of ACF formation [2].
  • 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) [19].
  • The effect of PGE(2) was reproduced by the E prostanoid (EP)1 receptor agonist 17-trinor-PGE(2), and the EP1/EP3 agonist, sulprostone, but not the EP2 receptor agonist, butaprost [20].

Physical interactions of Ptger1

  • These results suggest that PGE2 contributes to colon carcinogenesis through binding to the EP1 receptor [21].

Regulatory relationships of Ptger1

  • The PGE2-induced phase shift is inhibited by the EP1 antagonist SC-51322 [22].
  • RT-PCR revealed that EP1, EP2, and EP3 were expressed in rat calvariae and that osteoblastic cells (MC3T3-E1) expressed EP1 and EP2 [23].

Other interactions of Ptger1


Analytical, diagnostic and therapeutic context of Ptger1


  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. 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]
  3. 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]
  4. Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity. Kawano, T., Anrather, J., Zhou, P., Park, L., Wang, G., Frys, K.A., Kunz, A., Cho, S., Orio, M., Iadecola, C. Nat. Med. (2006) [Pubmed]
  5. Prostaglandin E receptor EP1 controls impulsive behavior under stress. Matsuoka, Y., Furuyashiki, T., Yamada, K., Nagai, T., Bito, H., Tanaka, Y., Kitaoka, S., Ushikubi, F., Nabeshima, T., Narumiya, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. Stock, J.L., Shinjo, K., Burkhardt, J., Roach, M., Taniguchi, K., Ishikawa, T., Kim, H.S., Flannery, P.J., Coffman, T.M., McNeish, J.D., Audoly, L.P. J. Clin. Invest. (2001) [Pubmed]
  12. Cyclooxygenase-2-derived prostaglandin E2 promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor-mediated activation of the epidermal growth factor receptor and Akt. Han, C., Wu, T. J. Biol. Chem. (2005) [Pubmed]
  13. 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]
  14. Characterization of prostanoid receptors in podocytes. Bek, M., Nüsing, R., Kowark, P., Henger, A., Mundel, P., Pavenstädt, H. J. Am. Soc. Nephrol. (1999) [Pubmed]
  15. Cellular localization of mRNAs for prostaglandin E receptor subtypes in mouse gastrointestinal tract. Morimoto, K., Sugimoto, Y., Katsuyama, M., Oida, H., Tsuboi, K., Kishi, K., Kinoshita, Y., Negishi, M., Chiba, T., Narumiya, S., Ichikawa, A. Am. J. Physiol. (1997) [Pubmed]
  16. Role of prostaglandin E receptor subtypes in gastroduodenal HCO3- secretion. Takeuchi, K., Aihara, E., Hayashi, M., Sasaki, Y. Medicinal chemistry (Sh⁻ariqah, United Arab Emirates) (2005) [Pubmed]
  17. Effects of UVB on E prostanoid receptor expression in murine skin. Tober, K.L., Thomas-Ahner, J.M., Kusewitt, D.F., Oberyszyn, T.M. J. Invest. Dermatol. (2007) [Pubmed]
  18. Impaired adrenocorticotropic hormone response to bacterial endotoxin in mice deficient in prostaglandin E receptor EP1 and EP3 subtypes. Matsuoka, Y., Furuyashiki, T., Bito, H., Ushikubi, F., Tanaka, Y., Kobayashi, T., Muro, S., Satoh, N., Kayahara, T., Higashi, M., Mizoguchi, A., Shichi, H., Fukuda, Y., Nakao, K., Narumiya, S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. 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]
  20. Regulation of prostaglandin endoperoxide synthase-2 and IL-6 expression in mouse bone marrow-derived mast cells by exogenous but not endogenous prostanoids. Diaz, B.L., Fujishima, H., Kanaoka, Y., Urade, Y., Arm, J.P. J. Immunol. (2002) [Pubmed]
  21. COX-2 and iNOS, good targets for chemoprevention of colon cancer. Watanabe, K., Kawamori, T., Nakatsugi, S., Wakabayashi, K. Biofactors (2000) [Pubmed]
  22. Resetting of peripheral circadian clock by prostaglandin E2. Tsuchiya, Y., Minami, I., Kadotani, H., Nishida, E. EMBO Rep. (2005) [Pubmed]
  23. 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]
  24. Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent manner after stimulation with titanium particles. Wei, X., Zhang, X., Zuscik, M.J., Drissi, M.H., Schwarz, E.M., O'Keefe, R.J. J. Bone Miner. Res. (2005) [Pubmed]
  25. 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]
  26. Combined effects of prostaglandin E receptor subtype EP1 and subtype EP4 antagonists on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice. Kitamura, T., Itoh, M., Noda, T., Tani, K., Kobayashi, M., Maruyama, T., Kobayashi, K., Ohuchida, S., Sugimura, T., Wakabayashi, K. Cancer Sci. (2003) [Pubmed]
  27. Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor. Guan, Y., Zhang, Y., Breyer, R.M., Fowler, B., Davis, L., Hébert, R.L., Breyer, M.D. J. Clin. Invest. (1998) [Pubmed]
  28. SC-19220, antagonist of prostaglandin E2 receptor EP1, inhibits osteoclastogenesis by RANKL. Tsujisawa, T., Inoue, H., Nishihara, T. J. Bone Miner. Res. (2005) [Pubmed]
  29. Molecular characterization of the mouse prostanoid EP1 receptor gene. Båtshake, B., Nilsson, C., Sundelin, J. Eur. J. Biochem. (1995) [Pubmed]
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