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https://www.readbyqxmd.com/read/29791834/molecular-and-functional-sex-differences-of-noradrenergic-neurons-in-the-mouse-locus-coeruleus
#1
Bernard Mulvey, Dionnet L Bhatti, Sandeep Gyawali, Allison M Lake, Skirmantas Kriaucionis, Christopher P Ford, Michael R Bruchas, Nathaniel Heintz, Joseph D Dougherty
Preclinical work has long focused on male animals, though biological sex clearly influences risk for certain diseases, including many psychiatric disorders. Such disorders are often treated by drugs targeting the CNS norepinephrine system. Despite roles for noradrenergic neurons in behavior and neuropsychiatric disease models, their molecular characterization has lagged. We profiled mouse noradrenergic neurons in vivo, defining over 3,000 high-confidence transcripts expressed therein, including druggable receptors...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29752406/the-prostaglandin-e-2-receptor-ep3-controls-cc-chemokine-ligand-mediated-neuropathic-pain-induced-by-mechanical-nerve-damage
#2
Elsa-Marie Treutlein, Katharina Kern, Andreas Weigert, Neda Tarighi, Claus-Dieter Schuh, Rolf M Nüsing, Yannick Schreiber, Nerea Ferreirós, Bernhard Brüne, Gerd Geisslinger, Sandra Pierre, Klaus Scholich
Prostaglandin (PG) E2 is an important lipid mediator that is involved in several pathophysiological processes contributing to fever, inflammation and pain. Previous studies have shown that early and continuous application of non-steroidal anti-inflammatory drugs significantly reduces pain behavior in the spared nerve injury (SNI) model for trauma-induced neuropathic pain. However, the role of PGE2 and its receptors in the development and maintenance of neuropathic pain is incompletely understood, but may help inform strategies for pain management...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29735520/identification-of-specific-components-of-the-eicosanoid-biosynthetic-and-signaling-pathway-involved-in-pathological-inflammation-during-intra-abdominal-infection-with-candida-albicans-and-staphylococcus-aureus
#3
Mélanie A C Ikeh, Paul L Fidel, Mairi C Noverr
Polymicrobial intra-abdominal infections (IAI) are a significant cause of morbidity and mortality, particularly when fungal pathogens are involved. Our experimental murine model of IAI involving intra-peritoneal inoculation of Candida albicans and Staphylococcus aureus results in synergistic lethality (∼80%) due to exacerbated inflammation. Monomicrobial infection results in no mortality despite similar microbial burden and dissemination as a co-infection. In the co-infection model, the immunomodulatory eicosanoid, prostaglandin E2 (PGE2 ) was determined to be necessary and sufficient to induce mortality implicating PGE2 as the central mediator of the amplified inflammatory response...
May 7, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29700097/prostaglandin-e2-receptor-3-ep3-signaling-is-induced-in-placentas-with-unexplained-recurrent-pregnancy-losses-urpl
#4
Yao Ye, Aurelia Vattai, Nina Ditsch, Christina Kuhn, Martina Rahmeh, Sven Mahner, Myriam Ripphahn, Roland Immler, Markus Sperandio, Udo Jeschke, Viktoria von Schoenfeldt
Although an inflammatory microenvironment is required for successful implantation, an inflammatory overreaction is one of the causes of unexplained recurrent pregnancy losses (uRPL). Prostaglandin E2 (PGE2) plays a pivotal role in regulating immune balance during early pregnancy and it can stimulate inflammatory reactions via EP3. However, the role of PGE2 receptor signaling in the uRPL remains unknown. We aimed to investigate whether prostaglandin E2 receptor 3 (EP3) signaling is involved in the mechanism of uRPL...
April 26, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29669171/prostaglandin-analogues-and-nitric-oxide-contribution-in-the-treatment-of-ocular-hypertension-and-glaucoma
#5
REVIEW
Francesco Impagnatiello, Elena Bastia, Nicoletta Almirante, Stefania Brambilla, Brigitte Duquesroix, Angela C Kothe, Michael V W Bergamini
In patients with ocular hypertension or glaucoma all treatments aim at lowering intraocular pressure (IOP) by modulating aqueous humor (AH) production and/or uveoscleral and trabecular meshwork /Schlemm's canal AH drainage. Prostaglandin (PG) analogues are considered the 'gold standard', and are the most frequently used IOP-lowering agents. Recent data support an important role of nitric oxide (NO) in regulating IOP. Thus novel PG analogues carrying a NO-donating moiety were recently advanced. Latanoprostene bunod (LBN) and NCX 470, respectively a NO-donating derivative of latanoprost and bimatoprost, are examples of such compounds...
April 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29661238/ep3-prostaglandin-e2-receptor-3-expression-is-a-prognostic-factor-for-progression-free-and-overall-survival-in-sporadic-breast-cancer
#6
Anna Semmlinger, Viktoria von Schoenfeldt, Verena Wolf, Alexandra Meuter, Theresa Maria Kolben, Thomas Kolben, Christine Zeder-Goess, Florian Weis, Julia Gallwas, Rachel Wuerstlein, Kerstin Hermelink, Elisa Schmoeckel, Nadia Harbeck, Doris Mayr, Sven Mahner, Udo Jeschke, Nina Ditsch
BACKGROUND: In various cancers, overexpression of cyclooxygenase (COX)-2 and elevated prostaglandin (PG) E2 synthesis have been associated with tumor development and progression. The potential of COX-2 inhibitors in cancer prevention and treatment has been shown repeatedly; however, their clinical use is limited due to toxicity. PGE2 signals via EP receptors 1-4, whose functions are analyzed in current research in search for targeted anti-PG therapies. EP2 and EP4 rather promote tumorigenesis, while the role of EP3, especially in breast cancer, is not yet clear and both pro- and anti-tumorigenic effects have been described...
April 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29599139/protective-role-of-mpges-1-microsomal-prostaglandin-e-synthase-1-derived-pge-2-prostaglandin-e2-and-the-endothelial-ep4-prostaglandin-e-receptor-in-vascular-responses-to-injury
#7
Huifeng Hao, Sheng Hu, Qing Wan, Chuansheng Xu, Hong Chen, Liyuan Zhu, Zhenyu Xu, Jian Meng, Richard M Breyer, Nailin Li, De-Pei Liu, Garret A FitzGerald, Miao Wang
OBJECTIVE: Deletion of mPGES-1 (microsomal prostaglandin E synthase-1)-an anti-inflammatory target alternative to COX (cyclooxygenase)-2-attenuates injury-induced neointima formation in mice. This is attributable to the augmented levels of PGI2 (prostacyclin)-a known restraint of the vascular response to injury, acting via IP (I prostanoid receptor). To examine the role of mPGES-1-derived PGE2 (prostaglandin E2) in vascular remodeling without the IP. APPROACH AND RESULTS: Mice deficient in both IP and mPGES-1 (DKO [double knockout] and littermate controls [IP KO (knockout)]) were subjected to angioplasty wire injury...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29596308/ep4-as-a-therapeutic-target-for-aggressive-human-breast-cancer
#8
REVIEW
Mousumi Majumder, Pinki Nandi, Ahmed Omar, Kingsley Chukwunonso Ugwuagbo, Peeyush K Lala
G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis...
March 29, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29593850/systemic-delivery-of-selective-ep1-and-ep3-receptor-antagonists-attenuates-pentylenetetrazole-induced-seizures-in-mice
#9
Cristina R Reschke, Alice B Poersch, Cíntia J Masson, Ana C Jesse, Joseane R Marafiga, Quéli F Lenz, Mauro S Oliveira, David C Henshall, Carlos F Mello
Neuroinflammation plays a major role in brain excitability and may contribute to the development of epilepsy. Prostaglandin E2 (PGE2 ) is a direct mediator of inflammatory responses and, through EP receptors, plays an important role in neuronal excitability. Pharmacological evidence supports that centrally-administered EP1 and EP3 receptor antagonists reduced acutely evoked seizures in rats. Translation of these findings would benefit from evidence of efficacy with a more clinically relevant route of delivery and validation in another species...
2018: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/29588339/selective-prostacyclin-receptor-agonist-selexipag-in-contrast-to-prostacyclin-analogs-does-not-evoke-paradoxical-vasoconstriction-of-rat-femoral-artery
#10
Keith Morrison, Franck Haag, Roland Ernst, Marc Iglarz, Martine Clozel
Selexipag is a selective non-prostanoid prostacyclin (PGI2 ) receptor (IP receptor) agonist that is approved for the treatment of pulmonary arterial hypertension (PAH). In contrast to selexipag, PGI2 analogs used in the clinic are non-selective agonists at prostanoid receptors and can also activate contractile EP3 receptors. Leg pain is a common side effect in patients receiving treatment with PGI2 analogs and peripheral vasoconstriction can be responsible for side effects related to muscular ischemia. This study tested the hypothesis that PGI2 analogs could cause paradoxical vasoconstriction of the femoral artery via EP3 receptor activation but that only vasorelaxation would be observed in response to selexipag and its active metabolite ACT-333679...
March 27, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29574261/the-expression-of-trpv-channels-prostaglandin-e2-and-pro-inflammatory-cytokines-during-behavioural-fever-in-fish
#11
Sebastian Boltana, Nataly Sanhueza, Andrea Donoso, Andrea Aguilar, Diego Crespo, Daniela Vergara, Gabriel Arriagada, Byron Morales-Lange, Luis Mercado, Sonia Rey, Lluis Tort, Simon Mackenzie
A fever, or increased body temperature, is a symptom of inflammation, which is a complex defence reaction of the organism to pathogenic infections. After pathogens enter the body, immune cells secrete a number of agents, the functions of which stimulate the body to develop a functional immune and fever response. In mammals it is known that PGE2 is the principal mediator of fever. The extent to which PGE2 and other pro-inflammatory cytokines such as TNF-α, IL-6, or IL-1β could be involved in the induction of behavioural fever in fish remains to be clarified...
March 21, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29557255/neural-mechanisms-of-inflammation-induced-fever
#12
Anders Blomqvist, David Engblom
Fever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis. Here, we review the different hypotheses on how the presence of peripherally released pyrogenic substances can be signaled to the brain to elicit fever. We conclude that there is unequivocal evidence for a humoral signaling pathway by which proinflammatory cytokines, through their binding to receptors on brain endothelial cells, evoke fever by eliciting prostaglandin E2 synthesis in these cells...
March 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/29522761/overexpression-of-prostaglandin-e2-ep4-receptor-improves-cardiac-function-after-myocardial-infarction
#13
Timothy D Bryson, Xiaosong Gu, Remonda M Khalil, Safa Khan, Liping Zhu, Jiang Xu, Edward Peterson, Xiao-Ping Yang, Pamela Harding
BACKGROUND: Prostaglandin E2 (PGE2 ) signals through 4 separate G-protein coupled receptor sub-types to elicit a variety of physiologic and pathophysiological effects. We recently reported that PGE2 via its EP3 receptor could reduce cardiac contractility of isolated myocytes and the working heart preparation. We thus hypothesized that there is an imbalance in the EP3/EP4 ratio towards EP3 in the failing heart and that overexpression of EP4 in a mouse model of heart failure would improve cardiac function...
May 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29497417/the-possible-effect-of-b-cell-epitopes-of-epstein-barr-virus-early-antigen-membrane-antigen-latent-membrane-protein-1-and-2a-on-systemic-lupus-erythematosus
#14
Jianxin Tu, Xiaobing Wang, Guannan Geng, Xiangyang Xue, Xiangyang Lin, Xiaochun Zhu, Li Sun
This study was aimed to evaluate the role of B-cell epitopes of Epstein-Barr virus (EBV) Early antigen protein D (EA), envelope glycoprotein GP340/membrane antigen (MA), latent membrane protein (LMP)-1, and LMP-2A in systemic lupus erythematosus (SLE). B-cell epitopes were predicted by analyzing secondary structure, transmembrane domains, surface properties, and homological comparison. 60 female mice were randomized equally into 12 groups: 1-10 groups were immunized by epitope peptides (EPs) 1-10, respectively, while 11 and 12 groups were PBS and Keyhole limpet hemocyanin (KLH) control groups...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29488342/pge2-ep3-signaling-exacerbates-hippocampus-dependent-cognitive-impairment-after-laparotomy-by-reducing-expression-levels-of-hippocampal-synaptic-plasticity-related-proteins-in-aged-mice
#15
Jing-Yu Xiao, Bing-Rui Xiong, Wen Zhang, Wen-Chang Zhou, Hui Yang, Feng Gao, Hong-Bing Xiang, Anne Manyande, Xue-Bi Tian, Yu-Ke Tian
AIM: Multifactors contribute to the development of postoperative cognitive dysfunction (POCD), of which the most important mechanism is neuroinflammation. Prostaglandin E2 (PGE2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE2 and its receptors signaling pathway were involved in the pathophysiology of POCD. METHODS: Sixteen-month old male C57BL/6J mice were exposed to laparotomy...
February 27, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29416671/prostaglandin-receptor-ep3-regulates-cell-proliferation-and-migration-with-impact-on-survival-of-endometrial-cancer-patients
#16
Junyan Zhu, Fabian Trillsch, Doris Mayr, Christina Kuhn, Martina Rahmeh, Simone Hofmann, Marianne Vogel, Sven Mahner, Udo Jeschke, Viktoria von Schönfeldt
Background: Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. Methods: We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29408043/selectively-targeting-prostanoid-e-ep-receptor-mediated-cell-signalling-pathways-implications-for-lung-health-and-disease
#17
REVIEW
Leonard F Lebender, Laura Prünte, Nowshin N Rumzhum, Alaina J Ammit
Arachidonic acid is metabolized by cyclooxygenases (COX-1 and COX-2) into various prostanoids which exert different functions in mammalian physiology. One of these prostanoids, prostaglandin E2 (PGE2 ), interacts with four different G protein-coupled receptors, named EP1 , EP2 , EP3 and EP4 , to initiate different downstream signalling pathways. Prostanoid receptors are diversely expressed throughout different tissues all over the body and PGE2 is responsible for a large variety of beneficial and disadvantageous effects...
April 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29401613/receptor-specific-crosstalk-between-prostanoid-e-receptor-3-and-bombesin-receptor-subtype-3
#18
Yan Zhang, Yanfang Liu, Lehao Wu, Chao Fan, Zhiwei Wang, Xiuli Zhang, Amal Alachkar, Xinmiao Liang, Olivier Civelli
Bombesin receptor subtype 3 (BRS-3) is a GPCR that is expressed in the CNS, peripheral tissues, and tumors. Our understanding of BRS-3's role in physiology and pathophysiology is limited because its natural ligand is unknown. In an attempt to identify this ligand, we screened toad skin ( Bufo bufo gargarizans Cantor) extracts and identified prostaglandins as putative ligands. In BRS-3-transfected human embryonic kidney (HEK) cells, we found that prostaglandins, with prostaglandin E2 (PGE2) being the most potent, fulfill the pharmacologic criteria of affinity, selectivity, and specificity to be considered as agonists to the BRS-3 receptor...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29336505/signalling-transduction-events-involved-in-agonist-induced-pge2-ep4-receptor-externalization-in-cultured-rat-dorsal-root-ganglion-neurons
#19
W Ma, B St-Jacques
BACKGROUND: Prostaglandin E2 (PGE2) enriched in inflamed tissues contributes to chronic pain by sensitizing nociceptive dorsal root ganglion (DRG) neurons (nociceptors). Of four PGE2 receptors (EP1-4), EP4 plays a major role in PGE2-induced nociceptor sensitization. We have previously reported that PGE2 or EP4 agonists stimulated EP4 externalization in cultured DRG neurons and this event contributes to nociceptor sensitization. However, the signalling transduction events governing this event remain unknown...
May 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29251736/pge-2-ep-1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#20
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
March 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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