Disease relevance of PTGFR

• 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 [1].
• Fine mapping of the PTGFR gene to 1p31 region and mutation analysis in human breast cancer [2].
• PURPOSE: To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial [3].
• These results suggest that pertussis toxin-sensitive GTP-binding protein is involved in the coupling of PGF2 alpha receptor to phospholipase C in these cells [4].
• In this study, we evaluated the efficacy and toxicity of FP therapy in the gastric cancer cell lines MKN45, MKN28, and KATOIII and the colon cancer cell lines HCT116 and COLO320, and examined the relationship between the response to FP therapy and apoptosis [5].

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

• CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to latanoprost and superior to timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension [10].
• FP mRNA increases in the mouse uterus at preterm birth, whereas PGF2alpha concentrations do not increase, suggesting elevated uterine sensitivity to contractile agonists is one mechanism for preterm labour initiation [11].
• OBJECTIVE: To determine the short-term effects of latanoprost, a selective FP prostanoid receptor agonist, in Meniere's disease [12].

Biological context of PTGFR

• The PTGFR and PTGER3 genes mapped to chromosome 1 at positions 1p31.1 and 1p31.2, respectively, and PTGER2 gene mapped to chromosome band 5p13.1 [13].
• A cDNA clone coding for a functional human prostanoid FP receptor has been isolated from a uterus cDNA library [14].
• We propose that uteroglobin plays important roles in maintaining homeostasis in organs that are vulnerable to inadvertent stimulation of FP-mediated inflammatory response [9].
• Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor [15].
• Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy [16].

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].

References