4.6 Review

Recent advances in GPR35 pharmacology; 5-HIAA serotonin metabolite becomes a ligand

Related references

Note: Only part of the references are listed.
Article Gastroenterology & Hepatology

Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases

Chloe Michaudel et al.

Summary: This study identified a new mechanism linking tryptophan metabolism to intestinal inflammation and inflammatory bowel diseases (IBDs). Bringing back xanthurenic acid (XANA) and kynurenic acid (KYNA) has protective effects involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism in intestinal epithelial cells and CD4(+) T cells. Manipulating the endogenous metabolic pathway with aminoadipate aminotransferase (AADAT) may provide new therapeutic strategies for correcting tryptophan metabolism alterations in IBD.
Review Immunology

GPR35 and mediators from platelets and mast cells in neutrophil migration and inflammation

Marco De Giovanni et al.

Summary: Neutrophil recruitment to inflamed tissues is guided by various chemoattractant cues, including 5-HIAA acting on GPR35. This article explores the unique response profiles of GPR35 to 5-HIAA compared to other ligands. The role of serotonin and its metabolite 5-HIAA in vascular biology and leukocyte recruitment is summarized, along with the cooperation of platelet and mast cell-derived mediators in promoting neutrophil recruitment. The potential broader influences of the 5-HIAA-GPR35 system in immunity and disease are also discussed.

IMMUNOLOGICAL REVIEWS (2023)

Article Pharmacology & Pharmacy

Gpr35 shapes gut microbial ecology to modulate hepatic steatosis

Xin Wu et al.

Summary: The gut microbiome is influenced by host genetic and dietary factors, playing a role in regulating metabolic health and disease. In this study, G protein-coupled receptor 35 (Gpr35) was identified as a regulator of gut microbial ecology and susceptibility to obesity and hepatic steatosis in mice. Deficiency of Gpr35 resulted in a loss of goblet cells, remodeling of the gut microbiome, and worsened metabolic disturbance and hepatic steatosis induced by high-fat diet. The study also revealed a potential interaction between Ruminococcus gnavus and the high-fat diet in promoting hepatic steatosis through specific metabolites.

PHARMACOLOGICAL RESEARCH (2023)

Article Pharmacology & Pharmacy

G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

Xiaoli Wei et al.

Summary: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. G protein-coupled receptor 35 (GPR35) plays a role in metabolic stresses, but its role in NAFLD has been unknown. In this study, we found that hepatocyte GPR35 regulates hepatic cholesterol homeostasis and mitigates NASH. Overexpression of GPR35 protected against diet-induced steatohepatitis, while loss of GPR35 had the opposite effect. Activation of GPR35 with the agonist kynurenic acid (Kyna) suppressed steatohepatitis in mice.

ACTA PHARMACEUTICA SINICA B (2023)

Review Pharmacology & Pharmacy

GPR35: from enigma to therapeutic target

Graeme Milligan

Summary: Despite being poorly characterised, orphan G-protein-coupled receptor 35 (GPR35) has attracted significant interest as a therapeutic target. Differences in pharmacology between human and rodent orthologues of the receptor have restricted preclinical disease models, but recent developments in ligands, transgenic mouse models, and analysis of single-nucleotide polymorphisms (SNPs) have improved understanding and stimulated disease-targeted proof-of-concept studies. This opinion article provides new insights into the biology of GPR35 and discusses its therapeutic potential in various diseases.

TRENDS IN PHARMACOLOGICAL SCIENCES (2023)

Article Biochemistry & Molecular Biology

GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA

Marco De Giovanni et al.

Summary: The G-protein-coupled receptor GPR35 is upregulated in activated neutrophils and plays a crucial role in their migration. The platelet-derived serotonin metabolite 5-HIAA acts as a ligand for GPR35 and promotes neutrophil recruitment to sites of inflammation via platelets and mast cells.
Article Cell Biology

G-Protein Coupled Receptor 35 Induces Intervertebral Disc Degeneration by Mediating the Influx of Calcium Ions and Upregulating Reactive Oxygen Species

Zhe Chen et al.

Summary: This study reveals the critical role of GPR35 in mediating intervertebral disc degeneration (IDD) through mediating calcium ions influx and upregulating reactive oxygen species (ROS). The findings suggest the potential advantage of targeting GPR35 for the prevention and treatment of IDD.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2022)

Article Gastroenterology & Hepatology

Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Ester Pagano et al.

Summary: The study demonstrates that GPR35 on macrophages can enhance tumor growth by stimulating neoangiogenesis and tumor tissue remodeling. Deletion of GPR35 significantly reduces tumor growth caused by the mutant tumor suppressor adenomatous polyposis coli in inflammation-associated and spontaneous tumor models.
Article Immunology

Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity

Hassan Melhem et al.

Summary: This study reveals the critical role of Gpr35 in goblet cell function and its regulation of goblet cell numbers and microbiota balance through maintaining normal pyroptosis levels. It is essential for maintaining intestinal health and the symbiotic relationship between host and microbiota.

MUCOSAL IMMUNOLOGY (2022)

Article Pharmacology & Pharmacy

The GPR35 expression pattern is associated with overall survival in male patients with colorectal cancer

Tomasz Mackiewicz et al.

Summary: This study suggests that the expression of GPR35 is associated with survival rates in colorectal cancer patients and has prognostic value for male patients.

PHARMACOLOGICAL REPORTS (2022)

Article Orthopedics

Exercised accelerated the production of muscle-derived kynurenic acid in skeletal muscle and alleviated the postmenopausal osteoporosis through the Gpr35/NF?B p65 pathway

Tianshu Shi et al.

Summary: The serum level of muscle-derived kynurenic acid (Kyna) is lower in postmenopausal osteoporosis (PMOP) model mice. Exercise and exogenous Kyna treatment can alleviate the effects of PMOP through the Gpr35 receptor.

JOURNAL OF ORTHOPAEDIC TRANSLATION (2022)

Article Agriculture, Multidisciplinary

A Genomics-Based Semirational Approach for Expanding the Postbiotic Potential of Collagen Peptides Using Lactobacillaceae

Ji-Young Lee et al.

Summary: This study used a genomics-based approach to analyze collagen peptides produced from probiotic fermentation and found their potential as postbiotics. The digestion of collagen by different Lactobacillaceae species resulted in the production of unique peptides. One species produced collagen peptides that showed agonistic activities towards GPR35 and could repair intestinal epithelium through a specific signaling pathway. This study provides an effective strategy for screening collagen peptides for gut health.

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY (2022)

Article Biochemistry & Molecular Biology

Isoforms of GPR35 have distinct extracellular N-termini that allosterically modify receptor-transducer coupling and mediate intracellular pathway bias

Hannes Schihada et al.

Summary: The G protein-coupled receptor GPR35 is involved in oncogenic signaling, bacterial infections, and inflammatory bowel disease within the intestine. This study reveals that GPR35 has two isoforms with distinct promoters and alternative splicing. The longer isoform limits G protein activation but enhances receptor-beta-arrestin interaction. Structural analysis suggests that a disulfide bridge between the N-terminus and extracellular loop 3 is crucial for G protein activation, while an additional cysteine from the extended N-terminus of the longer isoform limits agonist-induced receptor-beta-arrestin2 interaction. The findings provide insights for developing isoform-specific GPR35 ligands for mechanism-based therapies.

JOURNAL OF BIOLOGICAL CHEMISTRY (2022)

Article Cell Biology

Insights into divalent cation regulation and G13-coupling of orphan receptor GPR35

Jia Duan et al.

Summary: This study reports the cryo-electron microscopy structure of GPR35 coupled with G(13) and bound to the anti-allergic drug lodoxamide. The structure reveals a novel divalent cation coordination site and a unique ionic regulatory mode of GPR35, providing insights into its ligand binding promiscuity. Structural comparison with other G protein subtypes-coupled GPCRs highlights significant movements in the G alpha(13) subunit and the GPR35 TM6 helix.

CELL DISCOVERY (2022)

Article Multidisciplinary Sciences

Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists

Gregory A. Wyant et al.

Summary: Kynurenic acid (KynA) has tissue-protective effects in ischemia models, and this study demonstrates that activation of GPR35 and interaction with ATPIF1 may be the underlying mechanism. These findings provide a rationale for developing specific GPR35 agonists for the treatment of ischemic diseases.

SCIENCE (2022)

Editorial Material Pharmacology & Pharmacy

GPR35, ally of the anti-ischemic ATPIF1-ATP synthase interaction

Salvatore Nesci

Summary: Mitochondrial ATP synthase synthesizes ATP for cellular functions, but it can also hydrolyze ATP under various conditions to re-energize the mitochondria. ATP synthase inhibitory factor 1 (ATPIF1) inhibits this hydrolysis process. Recent research has shown that G-protein-coupled receptor 35 (GPR35) is involved in this process, providing a new framework for the discovery of potential therapeutic molecules against ischemia/reperfusion (I/R) injury.

TRENDS IN PHARMACOLOGICAL SCIENCES (2022)

Article Pharmacology & Pharmacy

Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage

Di Wang et al.

Summary: Chemotherapy-induced intestinal damage is characterized by upregulation of the tryptophan-kynurenine-kynurenic acid axis metabolism, with AHR and GPR35 playing important roles in regulating intestinal integrity and inflammation. The discovery of vardenafil and linagliptin as potential therapeutics for alleviating chemotherapy-induced intestinal toxicity highlights the potential of targeting GPR35 and AHR in cancer therapy.

ACTA PHARMACEUTICA SINICA B (2021)

Article Oncology

Forecasting sensitive targets of the kynurenine pathway in pancreatic adenocarcinoma using mathematical modeling

Murad Alahdal et al.

Summary: A new mathematical model was established to identify sensitive targets in the kynurenine pathway in pancreatic adenocarcinoma, and these targets were confirmed through gene and protein expression responses. The model showed high predictive accuracy and reliability, providing evidence for potential treatment targets in PDAC.

CANCER SCIENCE (2021)

Article Chemistry, Medicinal

Structure-Activity Relationship Studies of Coumarin-like Diacid Derivatives as Human G Protein-Coupled Receptor-35 (hGPR35) Agonists and a Consequent New Design Principle

Lai Wei et al.

Summary: Novel coumarin-like diacid derivatives were designed and synthesized as potent agonists of human G-protein-coupled receptor 35 (hGPR35). Compounds with two acidic groups connected to a rigid aromatic scaffold displayed excellent potency, demonstrating a general strategy for designing and recognizing GPR35 agonists.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Biology

G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis

Annemarie Boleij et al.

Summary: GPR35 plays a crucial role in the response of colonic epithelial cells to BFT, and GPR35 deficiency can reduce the mortality and disease severity induced by ETBF in mice.

COMMUNICATIONS BIOLOGY (2021)

Article Biochemistry & Molecular Biology

GPR35 regulates osteogenesis via the Wnt/GSK3β/β-catenin signaling pathway

Yao Zhang et al.

Summary: The expression of GPR35 in bone marrow mesenchymal stem cells is suppressed in osteoporosis patients and mice, affecting osteogenic differentiation. GPR35 deficiency impairs the function of BMSCs, while overexpression contributes to osteogenesis. The synthetic GPR35 agonist zaprinast can reduce bone loss and promote bone generation, suggesting a potential novel treatment for osteoporosis.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2021)

Article Immunology

Rational design of innate defense regulator peptides as tumor vaccine adjuvants

Yaomei Tian et al.

Summary: This study presents a screening and evaluation system for IDR design, where the optimized DP7 recruited various immune cells and in combination with CpG induced immune responses. The composite adjuvant played a positive role in antigen uptake, dendritic cell function enhancement, and improvement of antibody and cellular immunity.

NPJ VACCINES (2021)

Article Biochemistry & Molecular Biology

Disruption of GPR35 Signaling in Bone Marrow-Derived Cells Does Not Influence Vascular Inflammation and Atherosclerosis in Hyperlipidemic Mice

Roland Baumgartner et al.

Summary: Studies on G-protein-coupled receptor-35 (GPR35) suggest that its expression does not directly impact macrophage activation, vascular inflammation, and the development of atherosclerosis, as indicated by experiments on GPR35KO and WT chimeric mice.

METABOLITES (2021)

Article Chemistry, Medicinal

G Protein-Coupled Receptor GPR35 Suppresses Lipid Accumulation in Hepatocytes

Li-Chiung Lin et al.

Summary: Experimental studies using various mouse models and a humanized GPR35 mouse model suggest that activation of the GPR35 receptor can effectively prevent and reverse lipid accumulation induced by liver X receptor stimulation. This finding highlights the potential value of targeting GPR35 in the treatment of fatty liver diseases.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2021)

Article Biochemistry & Molecular Biology

Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35

Mi-Jeong Kim et al.

BIOMOLECULES & THERAPEUTICS (2020)

Review Biochemistry & Molecular Biology

Kynurenic acid and cancer: facts and controversies

Katarzyna Walczak et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2020)

Article Multidisciplinary Sciences

Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance

Julian M. Yabut et al.

NATURE COMMUNICATIONS (2020)

Article Cardiac & Cardiovascular Systems

Inhibition of GPR35 Preserves Mitochondrial Function After Myocardial Infarction by Targeting Calpain 1/2

Ken Chen et al.

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY (2020)

Article Multidisciplinary Sciences

Activation of GPR35 protects against cerebral ischemia by recruiting monocyte-derived macrophages

Ozayra Sharmin et al.

SCIENTIFIC REPORTS (2020)

Article Chemistry, Medicinal

Therapeutic Opportunities and Challenges in Targeting the Orphan G Protein-Coupled Receptor GPR35

Tezz Quon et al.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2020)

Article Multidisciplinary Sciences

Combinatorial expression of GPCR isoforms affects signalling and drug responses

Maria Marti-Solano et al.

NATURE (2020)

Article Cell Biology

Protective effect of lodoxamide on hepatic steatosis through GPR35

So-Yeon Nam et al.

CELLULAR SIGNALLING (2019)

Article Biochemistry & Molecular Biology

Receptor selectivity between the G proteins Gα12 and Gα13 is defined by a single leucine-to-isoleucine variation

Amanda E. Mackenzie et al.

FASEB JOURNAL (2019)

Article Biochemistry & Molecular Biology

GPR35 promotes glycolysis, proliferation, and oncogenic signaling by engaging with the sodium potassium pump

Georg Schneditz et al.

SCIENCE SIGNALING (2019)

Article Peripheral Vascular Disease

The Orphan Receptor GPR35 Contributes to Angiotensin II-Induced Hypertension and Cardiac Dysfunction in Mice

Nina Divorty et al.

AMERICAN JOURNAL OF HYPERTENSION (2018)

Article Cell Biology

Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation

Leandro Z. Agudelo et al.

CELL METABOLISM (2018)

Article Immunology

Evidence for the Existence of a CXCL17 Receptor Distinct from GPR35

Nurul A. S. Binti Mohd Amir et al.

JOURNAL OF IMMUNOLOGY (2018)

Article Endocrinology & Metabolism

Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms

Kristoffer L. Egerod et al.

MOLECULAR METABOLISM (2018)

Article Gastroenterology & Hepatology

Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice

Shukkur M. Farooq et al.

DIGESTIVE DISEASES AND SCIENCES (2018)

Article Biotechnology & Applied Microbiology

Overexpression of GPR35 confers drug resistance in NSCLC cells by beta-arrestin/Akt signaling

Wei Wang et al.

ONCOTARGETS AND THERAPY (2018)

Review Biochemical Research Methods

Analysis and measurement of serotonin

Andras Szeitz et al.

BIOMEDICAL CHROMATOGRAPHY (2018)

Article Biotechnology & Applied Microbiology

Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer

Sara Ruiz-Pinto et al.

PHARMACOGENETICS AND GENOMICS (2017)

Article Pharmacology & Pharmacy

G protein-coupled receptor 35 contributes to mucosal repair in mice via migration of colonic epithelial cells

Takuya Tsukahara et al.

PHARMACOLOGICAL RESEARCH (2017)

Article Biochemistry & Molecular Biology

The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer

Ya Jie Guo et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2017)

Article Cell Biology

Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans

Maja Schlittler et al.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2016)

Article Pharmacology & Pharmacy

Functional G-protein-coupled receptor 35 is expressed by neurons in the CA1 field of the hippocampus

Manickavasagom Alkondon et al.

BIOCHEMICAL PHARMACOLOGY (2015)

Article Gastroenterology & Hepatology

Immunochip Analysis Identification of 6 Additional Susceptibility Loci for Crohn's Disease in Koreans

Suk-Kyun Yang et al.

INFLAMMATORY BOWEL DISEASES (2015)

Review Pharmacology & Pharmacy

G protein-coupled receptor 35: an emerging target in inflammatory and cardiovascular disease

Nina Divorty et al.

FRONTIERS IN PHARMACOLOGY (2015)

Article Immunology

Cutting Edge: GPR35/CXCR8 Is the Receptor of the Mucosal Chemokine CXCL17

Jose L. Maravillas-Montero et al.

JOURNAL OF IMMUNOLOGY (2015)

Article Biochemistry & Molecular Biology

Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways

Katarzyna Walczak et al.

AMINO ACIDS (2014)

Article Cardiac & Cardiovascular Systems

Hypoxia-inducible factor 1-induced G protein-coupled receptor 35 expression is an early marker of progressive cardiac remodelling

Veli-Pekka Ronkainen et al.

CARDIOVASCULAR RESEARCH (2014)

Article Biochemical Research Methods

Screening beta-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors

Craig Southern et al.

JOURNAL OF BIOMOLECULAR SCREENING (2013)

Article Endocrinology & Metabolism

Mast Cells in Human Adipose Tissue: Link with Morbid Obesity, Inflammatory Status, and Diabetes

Adeline Divoux et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2012)

Article Pharmacology & Pharmacy

Aspirin metabolites are GPR35 agonists

Huayun Deng et al.

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY (2012)

Article Pharmacology & Pharmacy

GPR35 Is a Target of the Loop Diuretic Drugs Bumetanide and Furosemide

Yuhua Yang et al.

PHARMACOLOGY (2012)

Article Multidisciplinary Sciences

Multiple tyrosine metabolites are GPR35 agonists

Huayun Deng et al.

SCIENTIFIC REPORTS (2012)

Article Pharmacology & Pharmacy

Antagonists of GPR35 Display High Species Ortholog Selectivity and Varying Modes of Action

Laura Jenkins et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2012)

Review Pharmacology & Pharmacy

Orthologue selectivity and ligand bias: translating the pharmacology of GPR35

Graeme Milligan

TRENDS IN PHARMACOLOGICAL SCIENCES (2011)

Article Biochemistry & Molecular Biology

GPR35 is a novel lysophosphatidic acid receptor

Saori Oka et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2010)

Article Biochemistry & Molecular Biology

Expression of functional GPR35 in human iNKT cells

Silvia Fallarini et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2010)

Article Biochemistry & Molecular Biology

Identification of genes related to heart failure using global gene expression profiling of human failing myocardium

Kyung-Duk Min et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2010)

Article Biochemistry & Molecular Biology

Kynurenic Acid Triggers Firm Arrest of Leukocytes to Vascular Endothelium under Flow Conditions

Marita C. Barth et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

Article Genetics & Heredity

Common variants at five new loci associated with early-onset inflammatory bowel disease

Marcin Imielinski et al.

NATURE GENETICS (2009)

Article Biochemistry & Molecular Biology

GPR35 is a functional receptor in rat dorsal root ganglion neurons

Hiroyuki Ohshiro et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2008)

Review Immunology

New developments in mast cell biology

Janet Kalesnikoff et al.

NATURE IMMUNOLOGY (2008)

Article Pharmacology & Pharmacy

5-Nitro-2-(3-Phenylpropylamino)benzoic Acid Is a GPR35 Agonist

Yasuhito Taniguchi et al.

PHARMACOLOGY (2008)

Article Pharmacology & Pharmacy

Inhibition of N-type calcium channels by activation of GPR35, an orphan receptor, heterologously expressed in rat sympathetic neurons

Juan Guo et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2008)

Article Pharmacology & Pharmacy

Kynurenine pathway metabolism in patients with osteoporosis after 2 years of drug treatment

Caroline M. Forrest et al.

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY (2006)

Article Biochemistry & Molecular Biology

Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35

Jinghong Wang et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2006)