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Gene Review

PTGER3  -  prostaglandin E receptor 3 (subtype EP3)

Homo sapiens

Synonyms: EP3, EP3-I, EP3-II, EP3-III, EP3-IV, ...
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Disease relevance of PTGER3


High impact information on PTGER3

  • Our results establish that PGE2 mediates fever generation in response to both exogenous and endogenous pyrogens by acting at the EP3 receptor [6].
  • Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3 [6].
  • CONCLUSIONS: The ECL carcinoid tumor cells of Mastomys seem to possess two subtypes of PGE receptor: EP2 linked to cAMP production and EP3 coupled with inhibitory guanosine 5'-triphosphate-binding proteins mediating the inhibition of cAMP production [7].
  • Copresence of prostaglandin EP2 and EP3 receptors on gastric enterochromaffin-like cell carcinoid in African rodents [7].
  • EP1 and EP3 mRNA expression predominates in the collecting duct and thick limb, respectively, where their stimulation reduces NaCl and water absorption, promoting natriuresis and diuresis [8].

Chemical compound and disease context of PTGER3


Biological context of PTGER3


Anatomical context of PTGER3

  • Four prostaglandin E2 receptor subtypes designated EP1, EP2, EP3, and EP4 have been shown to mediate a variety of effects of prostaglandin E2 (PGE2) on glomerular hemodynamics, tubular salt and water reabsorption, and on blood vessels in the human kidney [16].
  • The human EP3 receptor subtype protein was strongly expressed in glomeruli, Tamm-Horsfall negative late distal convoluted tubules, connecting segments, cortical and medullary collecting ducts, as well as in the media and the endothelial cells of arteries and arterioles [16].
  • To address this question, we determined the localization and expression of the PGE2 receptor subtypes (PTGER1-4) and the PGF2alpha receptor (PTGFR) in paired upper and lower segment myometrium, amnion, and choriodecidual samples throughout human pregnancy, with and without labor [17].
  • Long-term (24 h) incubation of mast cells with either PGE2 or butaprost (EP2 agonist), but not sulprostone (EP1/EP3 agonist), caused a significant reduction in the subsequent ability of PGE2 to inhibit histamine release [18].
  • PGE2 can elicit diverse actions within the uterus depending on the PGE2 receptors (EP1, EP2, EP3 and EP4) expressed [19].

Associations of PTGER3 with chemical compounds

  • Thus, while PGE2 activates MCs through EP3 receptors, it also counteracts Fc epsilonRI-mediated eicosanoid production through EP2 receptors and PKA, and blocks cytokine transcription [13].
  • A selective PGE2 receptor antagonist abolished the increased adhesion and the augmented alpha2beta1-integrin expression induced by both PGE2 and LTD4 [20].
  • The EP3/EP1-receptor agonist sulprostone failed to induce IL-6 release, suggesting an involvement of EP4-like receptors [21].
  • PGE2-mediated suppression of IP-10 synthesis was counteracted by adenylate cyclase inhibitor SQ22536 and protein kinase A inhibitor H-89, and PGE2 receptor EP4 antagonist AH23848B [22].
  • The EP2-selective agonist, butaprost (pEC50, 5.2+/-0.2), was an effective inhibitor of mediator release whereas the EP1/EP3 receptor agonist, sulprostone, and the EP1-selective agonist, 17-phenyl-trinor-PGE2, were ineffective [18].

Regulatory relationships of PTGER3

  • We found that the maturational effects of the lymphokine or 1,25[OH]2D3 were accompanied by a marked reduction in the PGE2-induced increase in cellular content of adenosine 3':5'-cyclic monophosphate (cAMP) and a shift in the dose-response curve consistent with a decrease in PGE2 receptor number or binding affinity [23].
  • The results suggest that activation of protein kinase C increases PTH-stimulated adenylate cyclase activity by actions on Gi and/or the catalytic subunit and decreases PGE2 responsiveness by a mechanism involving the PGE2 receptor [24].

Other interactions of PTGER3


Analytical, diagnostic and therapeutic context of PTGER3

  • Consistent with the RT-PCR results, immunohistochemistry confirmed the presence and, interestingly, showed nuclear localization of EP receptors in the myometrium with higher EP1 expression and lower expression of EP3 [19].
  • Pulp cells express mainly EP2, EP3 and EP1 receptors as analysed by RT-PCR [29].
  • 5. PCR was used to confirm the presence of mRNAs encoding the four human EP3 receptor variants in tissues of the human small intestine, heart and pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)[30]
  • Molecular cloning and expression of human EP3 receptors: evidence of three variants with differing carboxyl termini [30].
  • The EP3-receptor gene is expressed in various tissues with high expression in kidney and pancreas, as demonstrated by Northern blot analysis [31].


  1. Seminal plasma activates cyclooxygenase-2 and prostaglandin E2 receptor expression and signalling in cervical adenocarcinoma cells. Sales, K.J., Katz, A.A., Millar, R.P., Jabbour, H.N. Mol. Hum. Reprod. (2002) [Pubmed]
  2. DNA microarray analysis of gene expression profiles in deep endometriosis using laser capture microdissection. Matsuzaki, S., Canis, M., Vaurs-Barrière, C., Pouly, J.L., Boespflug-Tanguy, O., Penault-Llorca, F., Dechelotte, P., Dastugue, B., Okamura, K., Mage, G. Mol. Hum. Reprod. (2004) [Pubmed]
  3. Inhibition of interleukin-1beta-induced COX-2 and EP3 gene expression by sodium salicylate enhances pancreatic islet beta-cell function. Tran, P.O., Gleason, C.E., Robertson, R.P. Diabetes (2002) [Pubmed]
  4. Defective arachidonate release and PGE2 production in Gi alpha2-deficient intestinal and colonic subepithelial myofibroblasts. Edwards, R.A., Smock, A.Z. Inflamm. Bowel Dis. (2006) [Pubmed]
  5. Cloning and expression of a cDNA for mouse prostaglandin E receptor EP3 subtype. Sugimoto, Y., Namba, T., Honda, A., Hayashi, Y., Negishi, M., Ichikawa, A., Narumiya, S. J. Biol. Chem. (1992) [Pubmed]
  6. Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3. Ushikubi, F., Segi, E., Sugimoto, Y., Murata, T., Matsuoka, T., Kobayashi, T., Hizaki, H., Tuboi, K., Katsuyama, M., Ichikawa, A., Tanaka, T., Yoshida, N., Narumiya, S. Nature (1998) [Pubmed]
  7. Copresence of prostaglandin EP2 and EP3 receptors on gastric enterochromaffin-like cell carcinoid in African rodents. Naribayashi-Inomoto, Y., Ding, M., Nakata, H., Narumiya, S., Sugimoto, Y., Honda, A., Ichikawa, A., Chiba, T., Kinoshita, Y. Gastroenterology (1995) [Pubmed]
  8. G protein-coupled prostanoid receptors and the kidney. Breyer, M.D., Breyer, R.M. Annu. Rev. Physiol. (2001) [Pubmed]
  9. Prostaglandin E receptors in myometrial cells. Asbóth, G., Phaneuf, S., López Bernal, A.L. Acta physiologica Hungarica. (1997) [Pubmed]
  10. Chronic alcohol consumption accelerates fibrosis in response to cerulein-induced pancreatitis in rats. Deng, X., Wang, L., Elm, M.S., Gabazadeh, D., Diorio, G.J., Eagon, P.K., Whitcomb, D.C. Am. J. Pathol. (2005) [Pubmed]
  11. Functional evidence for interaction between prostaglandin EP3 and kappa-opioid receptor pathways in tactile pain induced by human immunodeficiency virus type-1 (HIV-1) glycoprotein gp120. Minami, T., Matsumura, S., Mabuchi, T., Kobayashi, T., Sugimoto, Y., Ushikubi, F., Ichikawa, A., Narumiya, S., Ito, S. Neuropharmacology (2003) [Pubmed]
  12. Pulmonary edema in association with an intravenous infusion of sulprostone. Stock, A., Jones, R., Chung, T., Fung, H.Y. Acta obstetricia et gynecologica Scandinavica. (1995) [Pubmed]
  13. Human mast cells express multiple EP receptors for prostaglandin E2 that differentially modulate activation responses. Feng, C., Beller, E.M., Bagga, S., Boyce, J.A. Blood (2006) [Pubmed]
  14. Prostaglandin E2 activates Src signaling in lung adenocarcinoma cell via EP3. Yamaki, T., Endoh, K., Miyahara, M., Nagamine, I., Thi Thu Huong, N., Sakurai, H., Pokorny, J., Yano, T. Cancer Lett. (2004) [Pubmed]
  15. Isoforms of the EP3 subtype of human prostaglandin E2 receptor transduce both intracellular calcium and cAMP signals. An, S., Yang, J., So, S.W., Zeng, L., Goetzl, E.J. Biochemistry (1994) [Pubmed]
  16. Immunolocalization of the four prostaglandin E2 receptor proteins EP1, EP2, EP3, and EP4 in human kidney. Morath, R., Klein, T., Seyberth, H.W., Nüsing, R.M. J. Am. Soc. Nephrol. (1999) [Pubmed]
  17. Regional expression of prostaglandin E2 and F2alpha receptors in human myometrium, amnion, and choriodecidua with advancing gestation and labor. Grigsby, P.L., Sooranna, S.R., Adu-Amankwa, B., Pitzer, B., Brockman, D.E., Johnson, M.R., Myatt, L. Biol. Reprod. (2006) [Pubmed]
  18. Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell degranulation. Kay, L.J., Yeo, W.W., Peachell, P.T. Br. J. Pharmacol. (2006) [Pubmed]
  19. Identification and localization of prostaglandin E2 receptors in upper and lower segment human myometrium during pregnancy. Astle, S., Thornton, S., Slater, D.M. Mol. Hum. Reprod. (2005) [Pubmed]
  20. Leukotriene D4-induced adhesion of Caco-2 cells is mediated by prostaglandin E2 and upregulation of alpha2beta1-integrin. Massoumi, R., Nielsen, C.K., Azemovic, D., Sjölander, A. Exp. Cell Res. (2003) [Pubmed]
  21. Mechanisms of prostaglandin E2-induced interleukin-6 release in astrocytes: possible involvement of EP4-like receptors, p38 mitogen-activated protein kinase and protein kinase C. Fiebich, B.L., Schleicher, S., Spleiss, O., Czygan, M., Hüll, M. J. Neurochem. (2001) [Pubmed]
  22. Cyclooxygenase-2 inhibitor enhances whereas prostaglandin E2 inhibits the production of interferon-induced protein of 10 kDa in epidermoid carcinoma A431. Kanda, N., Watanabe, S. J. Invest. Dermatol. (2002) [Pubmed]
  23. The adenosine 3':5'-cyclic monophosphate response to prostaglandin E2 is altered in U937 cells in association with maturational events induced by activated T lymphocytes and 1,25-dihydroxyvitamin D3. Goldring, S.R., Amento, E.P., Roelke, M.S., Krane, S.M. J. Immunol. (1986) [Pubmed]
  24. Protein kinase C differentially modulates PTH- and PGE2-sensitive adenylate cyclase in osteoblast-like cells. Freyaldenhoven, A.M., Gutierrez, G.E., Lifschitz, M.D., Katz, M.S. Am. J. Physiol. (1992) [Pubmed]
  25. Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents. Brueggemeier, R.W., Richards, J.A., Joomprabutra, S., Bhat, A.S., Whetstone, J.L. J. Steroid Biochem. Mol. Biol. (2001) [Pubmed]
  26. Tumor necrosis factor-alpha upregulates the prostaglandin E2 EP1 receptor subtype and the cyclooxygenase-2 isoform in cultured amnion WISH cells. Spaziani, E.P., Benoit, R.R., Tsibris, J.C., Gould, S.F., O'Brien, W.F. J. Interferon Cytokine Res. (1998) [Pubmed]
  27. Cyclooxygenase-2-dependent prostaglandin E2 down-regulates intercellular adhesion molecule-1 expression via EP2/EP4 receptors in interleukin-1beta-stimulated human gingival fibroblasts. Noguchi, K., Iwasaki, K., Shitashige, M., Endo, H., Kondo, H., Ishikawa, I. J. Dent. Res. (2000) [Pubmed]
  28. Distribution of prostaglandin IP and EP receptor subtypes and isoforms in platelets and human umbilical artery smooth muscle cells. Paul, B.Z., Ashby, B., Sheth, S.B. Br. J. Haematol. (1998) [Pubmed]
  29. Cytokine-induced prostaglandin E(2) production and cyclooxygenase-2 expression in dental pulp cells: downstream calcium signalling via activation of prostaglandin EP receptor. Chang, M.C., Chen, Y.J., Tai, T.F., Tai, M.R., Li, M.Y., Tsai, Y.L., Lan, W.H., Wang, Y.L., Jeng, J.H. International endodontic journal. (2006) [Pubmed]
  30. Molecular cloning and expression of human EP3 receptors: evidence of three variants with differing carboxyl termini. Regan, J.W., Bailey, T.J., Donello, J.E., Pierce, K.L., Pepperl, D.J., Zhang, D., Kedzie, K.M., Fairbairn, C.E., Bogardus, A.M., Woodward, D.F. Br. J. Pharmacol. (1994) [Pubmed]
  31. Splice variants of the human EP3 receptor for prostaglandin E2. Schmid, A., Thierauch, K.H., Schleuning, W.D., Dinter, H. Eur. J. Biochem. (1995) [Pubmed]
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