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Gene Review

PTGFR  -  prostaglandin F receptor (FP)

Homo sapiens

Synonyms: FP, PGF receptor, PGF2-alpha receptor, Prostaglandin F2-alpha receptor, Prostanoid FP receptor
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Disease relevance of PTGFR


High impact information on PTGFR

  • These results indicate that parturition is initiated when prostaglandin F2alpha interacts with FP in ovarian luteal cells of the pregnant mice to induce luteolysis [6].
  • Mice lacking the gene encoding the receptor for prostaglandin F2alpha (FP) developed normally but were unable to deliver normal fetuses at term [6].
  • Prostanoid FP receptor agonists selectively increase uveoscleral outflow and the prostamide analog bimatoprost alters trabecular and uveoscleral outflow [7].
  • Calcitriol also repressed the mRNA expression of the PG receptors EP2 and FP, providing a potential additional mechanism of suppression of the biological activity of PGs [8].
  • The biological effects of PGF2alpha are mediated via the G protein-coupled receptor FP; however, the molecular mechanism(s) of FP signaling that mediates inflammatory lipid mediator production remains unclear [9].

Chemical compound and disease context of PTGFR


Biological context of PTGFR


Anatomical context of PTGFR

  • 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].
  • The presence of EP1-EP4 and FP in the Fallopian tube was detected using immunostaining [18].
  • Co-localization studies showed that the endothelial cells stained positive for EP1-EP4 and FP and that co-localization was seen for EP4 and c-kit [18].
  • Here we report that, in NIH 3T3 fibroblasts and human uterine smooth muscle cells, FP signaling is mediated via multi-kinase pathways in a cell type-specific manner to activate NF-kappaB, thus stimulating the expression of cyclooxygenase-2 [9].
  • We have shown previously that melanocytes, which provide photoprotection to keratinocytes through the production of melanin, express several receptors for prostaglandins, including the PGE2 receptors EP1 and EP3 and the PGF2alpha receptor FP, and that PGF2alpha stimulates melanocyte dendricity [19].

Associations of PTGFR with chemical compounds

  • The aim of this study was to gain information about the localization of the receptors for PGE(2) (EP1-EP4) and PGF(2alpha) (FP) in the human Fallopian tube and their regulation following treatment with mifepristone [18].
  • Inhibition of L(p) by the FP selective agonist latanoprost was additive to inhibition of vasopressin action by the EP selective agonist sulprostone [20].
  • In contrast to the Ca(2+) signal transduced by other FP receptors, this renal FP receptor signals via a PT-sensitive mechanism that is not coupled to cell Ca(2+) [20].
  • We have examined the expression of three prostaglandin (PG) receptors, EP2, EP4, and FP, in a nonpigmented ciliary epithelial cell line (ODMCl-2) and in human ciliary muscle (HCM) cells [21].
  • All FP (e.g. travoprost acid, fluprostenol), IP (iloprost) and TP (SQ29548) receptor-specific ligands exhibited low affinity (Ki > or = 1 microM) [22].

Other interactions of PTGFR

  • FP prostanoid receptors are G-protein coupled receptors that mediate the actions of prostaglandin F2alpha [23].
  • Histologically, this protein (FP regulatory protein or FPRP) shows a distribution coinciding well with those cells and tissues that respond to PGF2alpha [24].
  • Our data suggest that PAR-2 mediates cutaneous pigmentation both through increased uptake of melanosomes by keratinocytes, as well as by release of PGE(2) and PGF(2alpha) that stimulate melanocyte dendricity through EP1, EP3, and FP receptors [25].
  • In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium [26].
  • EP1- and FP-mediated cross-desensitization of the alpha (alpha) and beta (beta) isoforms of the human thromboxane A2 receptor [27].

Analytical, diagnostic and therapeutic context of PTGFR

  • Nuclease protection assay showed that FP mRNA expression predominates in rabbit ovary and kidney [20].
  • In situ hybridization revealed that renal FP expression predominates in the cortical collecting duct (CCD) [20].
  • The mRNA expression of the prostaglandin F(2alpha) receptor (PTGFR), a uterine activating gene, is increased at labor and is required for uterine contractile activity in numerous animal models, although the signaling pathways responsible for this increased expression have not been identified [28].
  • RESULTS: RT-PCR generated DNA products of predicted sizes corresponding to the EP2, EP4, and FP receptors [29].
  • Hybridization of the PCR products with specific 32P-labeled probes and restriction digestion of the PCR products further confirmed that they were generated from the respective EP2, EP4, and FP mRNAs [29].


  1. Expression, localization, and signaling of prostaglandin F2 alpha receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogen-activated protein kinase signaling pathways. Sales, K.J., Milne, S.A., Williams, A.R., Anderson, R.A., Jabbour, H.N. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  2. Fine mapping of the PTGFR gene to 1p31 region and mutation analysis in human breast cancer. Sossey-Alaoui, K., Kitamura, E., Cowell, J.K. Int. J. Mol. Med. (2001) [Pubmed]
  3. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). Ohtsu, A., Shimada, Y., Shirao, K., Boku, N., Hyodo, I., Saito, H., Yamamichi, N., Miyata, Y., Ikeda, N., Yamamoto, S., Fukuda, H., Yoshida, S. J. Clin. Oncol. (2003) [Pubmed]
  4. Involvement of pertussis toxin-sensitive GTP-binding protein in prostaglandin F2 alpha- induced phosphoinositide hydrolysis in osteoblast-like cells. Miwa, M., Tokuda, H., Tsushita, K., Kotoyori, J., Takahashi, Y., Ozaki, N., Kozawa, O., Oiso, Y. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  5. Expression of p53 protein as a predictor of the response to 5-fluorouracil and cisplatin chemotherapy in human gastrointestinal cancer cell lines evaluated with apoptosis by use of thin layer collagen gel. Matsuhashi, N., Saio, M., Matsuo, A., Sugiyama, Y., Saji, S. Int. J. Oncol. (2004) [Pubmed]
  6. Failure of parturition in mice lacking the prostaglandin F receptor. Sugimoto, Y., Yamasaki, A., Segi, E., Tsuboi, K., Aze, Y., Nishimura, T., Oida, H., Yoshida, N., Tanaka, T., Katsuyama, M., Hasumoto, K., Murata, T., Hirata, M., Ushikubi, F., Negishi, M., Ichikawa, A., Narumiya, S. Science (1997) [Pubmed]
  7. The inflow and outflow of anti-glaucoma drugs. Woodward, D.F., Gil, D.W. Trends Pharmacol. Sci. (2004) [Pubmed]
  8. Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cells. Moreno, J., Krishnan, A.V., Swami, S., Nonn, L., Peehl, D.M., Feldman, D. Cancer Res. (2005) [Pubmed]
  9. Uteroglobin inhibits prostaglandin F2alpha receptor-mediated expression of genes critical for the production of pro-inflammatory lipid mediators. Mandal, A.K., Ray, R., Zhang, Z., Chowdhury, B., Pattabiraman, N., Mukherjee, A.B. J. Biol. Chem. (2005) [Pubmed]
  10. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Netland, P.A., Landry, T., Sullivan, E.K., Andrew, R., Silver, L., Weiner, A., Mallick, S., Dickerson, J., Bergamini, M.V., Robertson, S.M., Davis, A.A. Am. J. Ophthalmol. (2001) [Pubmed]
  11. Role of the prostaglandins in labour and prostaglandin receptor inhibitors in the prevention of preterm labour. Olson, D.M., Ammann, C. Front. Biosci. (2007) [Pubmed]
  12. Effects of intratympanic injection of latanoprost in Meniere's disease: a randomized, placebo-controlled, double-blind, pilot study. Rask-Andersen, H., Friberg, U., Johansson, M., Stjernschantz, J. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. (2005) [Pubmed]
  13. Chromosomal localization of the human prostanoid receptor gene family. Duncan, A.M., Anderson, L.L., Funk, C.D., Abramovitz, M., Adam, M. Genomics (1995) [Pubmed]
  14. Cloning and expression of a cDNA for the human prostanoid FP receptor. Abramovitz, M., Boie, Y., Nguyen, T., Rushmore, T.H., Bayne, M.A., Metters, K.M., Slipetz, D.M., Grygorczyk, R. J. Biol. Chem. (1994) [Pubmed]
  15. Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor. Neuschäfer-Rube, F., Engemaier, E., Koch, S., Böer, U., Püschel, G.P. Biochem. J. (2003) [Pubmed]
  16. Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy. Chen, X.B., Regan, J.W. Cell. Mol. Life Sci. (2006) [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 and F2{alpha} receptors in the human Fallopian tube before and after mifepristone treatment. Wånggren, K., Lalitkumar, P.G., Stavreus-Evers, A., Ståbi, B., Gemzell-Danielsson, K. Mol. Hum. Reprod. (2006) [Pubmed]
  19. Effects of PGF2alpha on human melanocytes and regulation of the FP receptor by ultraviolet radiation. Scott, G., Jacobs, S., Leopardi, S., Anthony, F.A., Learn, D., Malaviya, R., Pentland, A. Exp. Cell Res. (2005) [Pubmed]
  20. Characterization of a rabbit kidney prostaglandin F(2{alpha}) receptor exhibiting G(i)-restricted signaling that inhibits water absorption in the collecting duct. Hébert, R.L., Carmosino, M., Saito, O., Yang, G., Jackson, C.A., Qi, Z., Breyer, R.M., Natarajan, C., Hata, A.N., Zhang, Y., Guan, Y., Breyer, M.D. J. Biol. Chem. (2005) [Pubmed]
  21. Detection of EP2, EP4, and FP receptors in human ciliary epithelial and ciliary muscle cells. Mukhopadhyay, P., Geoghegan, T.E., Patil, R.V., Bhattacherjee, P., Paterson, C.A. Biochem. Pharmacol. (1997) [Pubmed]
  22. Cloned human EP1 prostanoid receptor pharmacology characterized using radioligand binding techniques. Sharif, N.A., Davis, T.L. J. Pharm. Pharmacol. (2002) [Pubmed]
  23. Cloning and localization of hFP(S): a six-transmembrane mRNA splice variant of the human FP prostanoid receptor. Vielhauer, G.A., Fujino, H., Regan, J.W. Arch. Biochem. Biophys. (2004) [Pubmed]
  24. Human chromosome 1 localization of the gene for a prostaglandin F2alpha receptor negative regulatory protein. Orlicky, D.J., Berry, R., Sikela, J.M. Hum. Genet. (1996) [Pubmed]
  25. Proteinase-activated receptor-2 stimulates prostaglandin production in keratinocytes: analysis of prostaglandin receptors on human melanocytes and effects of PGE2 and PGF2alpha on melanocyte dendricity. Scott, G., Leopardi, S., Printup, S., Malhi, N., Seiberg, M., Lapoint, R. J. Invest. Dermatol. (2004) [Pubmed]
  26. In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium. Senior, J., Sangha, R., Baxter, G.S., Marshall, K., Clayton, J.K. Br. J. Pharmacol. (1992) [Pubmed]
  27. EP1- and FP-mediated cross-desensitization of the alpha (alpha) and beta (beta) isoforms of the human thromboxane A2 receptor. Kelley-Hickie, L.P., Kinsella, B.T. Br. J. Pharmacol. (2004) [Pubmed]
  28. The Interleukin 1beta-Induced Expression of Human Prostaglandin F2alpha Receptor Messenger RNA in Human Myometrial-Derived ULTR Cells Requires the Transcription Factor, NFkappaB. Zaragoza, D.B., Wilson, R.R., Mitchell, B.F., Olson, D.M. Biol. Reprod. (2006) [Pubmed]
  29. Expression of prostaglandin receptors EP4 and FP in human lens epithelial cells. Mukhopadhyay, P., Bhattacherjee, P., Andom, T., Geoghegan, T.E., Andley, U.P., Paterson, C.A. Invest. Ophthalmol. Vis. Sci. (1999) [Pubmed]
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