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https://www.readbyqxmd.com/read/27777084/crosstalk-between-the-gut-and-the-liver-via-susceptibility-loci-novel-advances-in-inflammatory-bowel-disease-and-autoimmune-liver-disease
#1
Xinyang Li, Jun Shen, Zhihua Ran
Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic, relapsing intestinal inflammation. Autoimmune liver disease (AILD) may be involved in IBD as an extra-intestinal manifestation (EIM). Epidemiologic and anatomic evidence have demonstrated an intimate crosstalk between the gut and the liver. In this review, we briefly introduced nine groups of susceptibility loci shared by inflammatory bowel and autoimmune liver disease for the first time. The genome-wide association studies (GWAS) evidence of pathways involving crosstalk between the gut and the liver is clarified and explained...
October 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27755520/-the-kynurenic-acid-hypothesis-a-new-look-at-etiopathogenesis-and-treatment-of-schizophrenia
#2
Marta Flis, Kinga Szymona, Justyna Morylowska-Topolska, Anna Urbańska, Paweł Krukow, Martyna Kandefer-Szerszeń, Barbara Zdzisińska, Ewa M Urbańska, Hanna Karakuła-Juchnowicz
Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan formed in the brain and in the periphery, known to block ionotropic glutamate receptors and α7 nicotinic receptors, and to act as a ligand of G protein-coupled GPR35 receptors and human aryl hydrocarbon (AHR) receptors. KYNA seems to modulate a number of mechanisms involved in the pathogenesis of schizophrenia including dopaminergic transmission in mesolimbic and mesocortical areas or glutamatemediated neurotransmission. The kynurenine hypothesis of schizophrenia links the occurrence of positive and negative symptoms of schizophrenia and cognitive impairments characteristic for the disease with the disturbances of kynurenine pathway function...
September 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27424891/label-free-cell-phenotypic-identification-of-d-luciferin-as-an-agonist-for-gpr35
#3
Heidi Hu, Huayun Deng, Ye Fang
D-Luciferin (also known as beetle or firefly luciferin) is one of the most widely used bioluminescent reporters for monitoring in vitro or in vivo luciferase activity. The identification of several natural phenols and thieno[3,2-b]thiophene-2-carboxylic acid derivatives as agonists for GPR35, an orphan G protein-coupled receptor, had motivated us to examine the pharmacological activity of D-Luciferin, given that it also contains phenol and carboxylic acid moieties. Here, we describe label-free cell phenotypic assays that ascertain D-Luciferin as a partial agonist for GPR35...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27350736/comprehensive-mutation-screening-for-10-genes-in-chinese-patients-suffering-very-early-onset-inflammatory-bowel-disease
#4
Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Xiao-Qin Li, Chun-Di Xu
AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease (VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients. METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing (NGS) based on an Illumina-Miseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10RA, IL-10RB, NOD2, FUT2, IL23R, GPR35, GPR65, TNFSF15, and ADAM30...
June 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27347941/computational-analysis-of-single-nucleotide-polymorphisms-associated-with-altered-drug-responsiveness-in-type-2-diabetes
#5
Valerio Costa, Antonio Federico, Carla Pollastro, Carmela Ziviello, Simona Cataldi, Pietro Formisano, Alfredo Ciccodicola
Type 2 diabetes (T2D) is one of the most frequent mortality causes in western countries, with rapidly increasing prevalence. Anti-diabetic drugs are the first therapeutic approach, although many patients develop drug resistance. Most drug responsiveness variability can be explained by genetic causes. Inter-individual variability is principally due to single nucleotide polymorphisms, and differential drug responsiveness has been correlated to alteration in genes involved in drug metabolism (CYP2C9) or insulin signaling (IRS1, ABCC8, KCNJ11 and PPARG)...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27131920/kynurenic-acid-and-zaprinast-induce-analgesia-by-modulating-hcn-channels-through-gpr35-activation
#6
Francesco Resta, Alessio Masi, Maria Sili, Annunziatina Laurino, Flavio Moroni, Guido Mannaioni
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have a key role in the control of cellular excitability. HCN2, a subgroup of the HCN family channels, are heavily expressed in small dorsal root ganglia (DRG) neurons and their activation seems to be important in the determination of pain intensity. Intracellular elevation of cAMP levels activates HCN-mediated current (Ih) and small DRG neurons excitability. GPR35, a Gi/o coupled receptor, is highly expressed in small DRG neurons, and we hypothesized that its activation, mediated by endogenous or exogenous ligands, could lead to pain control trough a reduction of Ih current...
September 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27064272/g-protein-coupled-receptor-35-mediates-human-saphenous-vein-vascular-smooth-muscle-cell-migration-and-endothelial-cell-proliferation
#7
Jennifer E McCallum, Amanda E Mackenzie, Nina Divorty, Carolyn Clarke, Christian Delles, Graeme Milligan, Stuart A Nicklin
Vascular smooth muscle cell (VSMC) migration and proliferation is central to neointima formation in vein graft failure following coronary artery bypass. However, there are currently no pharmacological interventions that prevent vein graft failure through intimal occlusion. It is hence a therapeutic target. Here, we investigated the contribution of GPR35 to human VSMC and endothelial cell (EC) migration, using a scratch-wound assay, and also the contribution to proliferation, using MTS and BrdU assays, in in vitro models using recently characterized human GPR35 ortholog-selective small-molecule agonists and antagonists...
2015: Journal of Vascular Research
https://www.readbyqxmd.com/read/27002183/metabolism-meets-immunity-the-role-of-free-fatty-acid-receptors-in-the-immune-system
#8
REVIEW
Elisa Alvarez-Curto, Graeme Milligan
There are significant numbers of nutrient sensing G protein-coupled receptors (GPCRs) that can be found in cells of the immune system and in tissues that are involved in metabolic function, such as the pancreas or the intestinal epithelium. The family of free fatty acid receptors (FFAR1-4, GPR84), plus a few other metabolite sensing receptors (GPR109A, GPR91, GPR35) have been for this reason the focus of studies linking the effects of nutrients with immunological responses. A number of the beneficial anti-inflammatory effects credited to dietary fats such as omega-3 fatty acids are attributed to their actions on FFAR4...
August 15, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/26384023/constitutive-activity-among-orphan-class-a-g-protein-coupled-receptors
#9
Adam L Martin, Michael A Steurer, Robert S Aronstam
The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin...
2015: PloS One
https://www.readbyqxmd.com/read/26232640/the-emerging-pharmacology-and-function-of-gpr35-in-the-nervous-system
#10
Amanda E Mackenzie, Graeme Milligan
G protein-coupled receptor 35 (GPR35) is an orphan G protein-coupled receptor (GPCR) that can be activated by kynurenic acid at high micromolar concentrations. A previously unappreciated mechanism of action of GPR35 has emerged as a Gαi/o-coupled inhibitor of synaptic transmission, a finding that has significant implications for the accepted role of kynurenic acid as a broad-spectrum antagonist of the NMDA, AMPA/kainite and α7 nicotinic receptors. In conjunction with previous findings that link agonism of GPR35 with significant reduction in nociceptive pain, GPR35 has emerged as a potential effector of regulation of mechanical sensitivity and analgesia of the Ret tyrosine kinase, and as a receptor involved in the transmission of anti-inflammatory effects of aspirin- potentially through affecting leukocyte rolling, adhesion and extravasation...
July 29, 2015: Neuropharmacology
https://www.readbyqxmd.com/read/25926795/the-therapeutic-potential-of-orphan-gpcrs-gpr35-and-gpr55
#11
REVIEW
Derek M Shore, Patricia H Reggio
The G protein-coupled receptor (GPCR) superfamily of integral proteins is the largest family of signal transducers, comprised of ∼1000 members. Considering their prevalence and functional importance, it's not surprising that ∼60% of drugs target GPCRs. Regardless, there exists a subset of the GPCR superfamily that is largely uncharacterized and poorly understood; specifically, more than 140 GPCRs have unknown endogenous ligands-the so-called orphan GPCRs. Orphan GPCRs offer tremendous promise, as they may provide novel therapeutic targets that may be more selective than currently known receptors, resulting in the potential reduction in side effects...
2015: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/25805994/g-protein-coupled-receptor-35-an-emerging-target-in-inflammatory-and-cardiovascular-disease
#12
REVIEW
Nina Divorty, Amanda E Mackenzie, Stuart A Nicklin, Graeme Milligan
G protein-coupled receptor 35 (GPR35) is an orphan receptor, discovered in 1998, that has garnered interest as a potential therapeutic target through its association with a range of diseases. However, a lack of pharmacological tools and the absence of convincingly defined endogenous ligands have hampered the understanding of function necessary to exploit it therapeutically. Although several endogenous molecules can activate GPR35 none has yet been confirmed as the key endogenous ligand due to reasons that include lack of biological specificity, non-physiologically relevant potency and species ortholog selectivity...
2015: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/25635858/genechip-expression-profiling-reveals-the-alterations-of-energy-metabolism-related-genes-in-osteocytes-under-large-gradient-high-magnetic-fields
#13
Yang Wang, Zhi-Hao Chen, Chun Yin, Jian-Hua Ma, Di-Jie Li, Fan Zhao, Yu-Long Sun, Li-Fang Hu, Peng Shang, Ai-Rong Qian
The diamagnetic levitation as a novel ground-based model for simulating a reduced gravity environment has recently been applied in life science research. In this study a specially designed superconducting magnet with a large gradient high magnetic field (LG-HMF), which can provide three apparent gravity levels (μ-g, 1-g, and 2-g), was used to simulate a space-like gravity environment. Osteocyte, as the most important mechanosensor in bone, takes a pivotal position in mediating the mechano-induced bone remodeling...
2015: PloS One
https://www.readbyqxmd.com/read/25542997/functional-g-protein-coupled-receptor-35-is-expressed-by-neurons-in-the-ca1-field-of-the-hippocampus
#14
Manickavasagom Alkondon, Edna F R Pereira, Spencer W Todd, William R Randall, Malcolm V Lane, Edson X Albuquerque
The G-protein-coupled receptor 35 (GPR35) was de-orphanized after the discovery that kynurenic acid (KYNA), an endogenous tryptophan metabolite, acts as an agonist of this receptor. Abundant evidence supports that GPR35 exists primarily in peripheral tissues. Here, we tested the hypothesis that GPR35 exists in the hippocampus and influences the neuronal activity. Fluorescence immunohistochemical staining using an antibody anti-NeuN (a neuronal marker), an antibody anti-GFAP (a glial marker), and an antibody anti-GPR35 revealed that neurons in the stratum oriens, stratum pyramidale, and stratum radiatum of the CA1 field of the hippocampus express GPR35...
February 15, 2015: Biochemical Pharmacology
https://www.readbyqxmd.com/read/25489960/immunochip-analysis-identification-of-6-additional-susceptibility-loci-for-crohn-s-disease-in-koreans
#15
COMPARATIVE STUDY
Suk-Kyun Yang, Myunghee Hong, Hyunchul Choi, Wanting Zhao, Yusun Jung, Talin Haritunians, Byong Duk Ye, Kyung-Jo Kim, Sang Hyoung Park, Inchul Lee, Won Ho Kim, Jae Hee Cheon, Young-Ho Kim, Byung Ik Jang, Hyun-Soo Kim, Jai Hyun Choi, Ja Seol Koo, Ji Hyun Lee, Sung-Ae Jung, Hyoung Doo Shin, Daehee Kang, Hee-Shang Youn, Kent D Taylor, Jerome I Rotter, Jianjun Liu, Dermot P B McGovern, Kyuyoung Song
BACKGROUND: Crohn's disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population. METHODS: Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls...
January 2015: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/25443745/on-the-toxicity-of-kynurenic-acid-in-vivo-and-in-vitro
#16
Waldemar A Turski, Joanna Małaczewska, Sebastian Marciniak, Jerzy Bednarski, Michał P Turski, Mirosław Jabłoński, Andrzej K Siwicki
BACKGROUND: Kynurenic acid (KYNA), a tryptophan metabolite is an antagonist of ionotropic glutamate receptors and alpha-7 nicotinic receptor. Moreover, it is an agonist of G-protein receptor GPR35. Its neuroprotective, anticonvulsant, anti-inflammatory and antioxidant activity was documented. KYNA is present in food and herbal medicines. However, the data on effects induced by a long-lasting treatment with KYNA is lacking. The aim of the study was the assessment of toxicity of a prolonged administration of KYNA in rodents...
December 2014: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/25411203/cutting-edge-gpr35-cxcr8-is-the-receptor-of-the-mucosal-chemokine-cxcl17
#17
José L Maravillas-Montero, Amanda M Burkhardt, Peter A Hevezi, Christina D Carnevale, Martine J Smit, Albert Zlotnik
Chemokines are chemotactic cytokines that direct the traffic of leukocytes and other cells in the body. Chemokines bind to G protein-coupled receptors expressed on target cells to initiate signaling cascades and induce chemotaxis. Although the cognate receptors of most chemokines have been identified, the receptor for the mucosal chemokine CXCL17 is undefined. In this article, we show that GPR35 is the receptor of CXCL17. GPR35 is expressed in mucosal tissues, in CXCL17-responsive monocytes, and in the THP-1 monocytoid cell line...
January 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25286653/the-in-vitro-effect-of-kynurenic-acid-on-the-rainbow-trout-oncorhynchus-mykiss-leukocyte-and-splenocyte-activity
#18
J Małaczewska, A K Siwicki, R Wójcik, W A Turski, E Kaczorek
Kynurenic acid (KYNA), an endogenous neuroprotectant formed along the kynurenine pathway of tryptophan degradation, is a selective ligand of the GPR35 receptor, which can be found on the surface of various populations of human immune cells. In infections and inflammations, KYNA produces an anti-inflammatory effect through this receptor, by depressing the synthesis of reactive oxygen species and pro-inflammatory cytokines. However, it is still unrecognized whether receptors for kynurenic acid are also localized on immune cells of poikilothermic animals, or whether KYNA is able to affect these cells...
2014: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/25150870/g-protein-coupled-receptor-mutations-and-human-genetic-disease
#19
REVIEW
Miles D Thompson, Geoffrey N Hendy, Maire E Percy, Daniel G Bichet, David E C Cole
Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1))...
2014: Methods in Molecular Biology
https://www.readbyqxmd.com/read/25040314/presence-and-content-of-kynurenic-acid-in-animal-feed
#20
M P Turski, W Zgrajka, A K Siwicki, P Paluszkiewicz
Kynurenic acid (KYNA) was found to be an antagonist of iontropic glutamate receptors and alpha7 nicotinic acetylcholine receptors. Furthermore, it was documented that KYNA is an agonist of G-protein coupled GPR35 receptors which are mainly present in the gastrointestinal tract. It was also found that KYNA is present in the gastrointestinal tract and that its concentration gradually increases along it. The origin of KYNA in the gastrointestinal tract is not known. Both might be synthesized from tryptophan in it or absorbed from food and other dietary products...
February 2015: Journal of Animal Physiology and Animal Nutrition
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