Disease relevance of PTGER3

• The aims of this study were to investigate the effect of seminal plasma and PGE2 on the expression of COX-2 and expression and signalling of the PGE2 receptor subtypes (EP1-EP4) in HeLa (cervical adenocarcinoma) cells [1].
• In addition, two potential negative regulators of aromatase expression, chicken ovalbumin upstream promoter transcription factor 2 (COUP-TF2) and prostaglandin E2 receptor subtype EP3 (PGE2EP3), were downregulated in endometriosis epithelial cells, which might result in increased local production of estrogen in endometriosis epithelial cells [2].
• Misoprostol, an EP3 agonist, inhibited glucose-induced insulin secretion from islets, an event that was prevented by preincubation with pertussis toxin, by decreasing cAMP [3].
• Finally, treatment of Gi alpha2-/- mice with the EP4-specific PGE2 receptor agonist ONO-AE1-329 significantly decreased the severity of established colitis [4].
• Northern blot analysis demonstrated that the EP3 mRNA is expressed abundantly in kidney, uterus, and mastocytoma P-815 cells and in a lesser amount in brain, thymus, lung, heart, stomach, and spleen [5].

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

• Sulprostone (EP3 > EP1) did not stimulate adenylyl cyclase activity per se, but inhibited forskolin-stimulated adenylyl cyclase in a pertussis toxin (PT) sensitive way [9].
• Fibrosis was significantly induced in the EP3 rats versus EP1, CP1, and CP3 by histology, hydroxyproline content, and mRNA expression for collagen alpha1(1) and procollagen alpha2(1) [10].
• 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 [11].
• Recent evidence suggests that pulmonary hypertension following the administration of prostaglandins may result from stimulation of an EP3 or thromboxane receptor in the pulmonary artery [12].

Biological context of PTGER3

• An EP3 receptor-selective agonist, AE-248, mimicked PGE2-mediated ERK phosphorylation, exocytosis, and eicosanoid formation [13].
• A specific antagonist against EP3 abrogated the cell growth and Src activation in the cells stimulated with PGE2 [14].
• Recently, we have reported that a PGE2 receptor, EP3 is involved in appearance of malignant phenotype of a lung adenocarcinoma cell (A549 cell) [14].
• The dual signal transduction pathways and distinctive tissue distribution of isoforms of the EP3 receptor are consistent with its mediation of diverse functions of PGE2 [15].
• Distinct cDNA clones encoding five isoforms of the EP3 receptor were isolated from a human uterus cDNA library [15].

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

• We assessed the functions of the EP receptors for PGE2 on cultured human MCs (hMCs). hMCs expressed the EP3, EP2, and EP4 receptors [13].
• Sulprostone, an EP3 agonist, did not alter aromatase activity levels [25].
• The purpose of this study was to investigate the effect of tumor necrosis factor-alpha (TNF-alpha) on the levels of cyclooxygenase, prostaglandin E2 production (PGE2), and expression of the PGE2 receptor subtype EP1 in amnion WISH cell culture [26].
• Sulprostone, an EP1/EP3 agonist, had no effect on IL-1beta-elicited ICAM-1 expression [27].
• The IP receptor, which binds prostacyclin and couples to stimulation of adenylyl cyclase, and three isoforms of the inhibitory EP3 receptor were equally expressed in platelets, HEL cells and umbilical artery smooth muscle cells [28].

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].

References