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The resulting NETs presumably activate platelets and coagulation factors, further contributing to the

September 2022 Sweet taste receptor agonists attenuate macrophage IL‐1β expression and eosinophilic inflammation linked to autophagy deficiency in myeloid cells "Background Eosinophilic inflammation is a hallmark

September 2022 GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome Here we demonstrate that GPR84 is highly upregulated in inflamed colon tissues of active ulcerative colitis These results define a unique role of GPR84 in innate immune cells and intestinal inflammation, and suggest

September 2022 Cell-Type-Specific Effects of the Ovarian Cancer G-Protein Coupled Receptor (OGR1) on Inflammation In fibroblasts, OGR1 inhibits myofibroblast differentiation and does not contribute to inflammation. However, in epithelial cells, OGR1 promotes epithelial to mesenchymal transition (EMT) and inflammation Our results suggest that strategies to selectively target OGR1 expression may represent a novel therapeutic

September 2022 Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following

August 2022 "The atypical chemokine receptor 1 (ACKR1) was discovered on erythrocytes as the Duffy blood group antigen ( Cutbush et al., 1950 ), also called Duffy-antigen/receptor for chemokines, or DARC ( Novitzky-Basso and Rot, 2012 ). Erythrocytes are terminally differentiated anuclear cells with no transcription and limited translation. Accordingly, within the erythroid lineage ACKR1 expression occurs first and is the highest in erythroblasts ( Duchene et al., 2017 ). Additionally, ACKR1 expression characterizes venular endothelial cells (ECs) ( Pruenster et al., 2009 ; Thiriot et al., 2017 ), including those lining bone marrow (BM) sinusoids ( Duchene et al., 2017 ). This well-established, distinctive pattern of cell expression has been directly challenged by a publication purporting ACKR1 expression in mouse BM by macrophages, but not erythroblasts and ECs, suggesting that macrophage ACKR1 engages its non-cognate ligand CD82 on hematopoietic stem cells (HSCs) to maintain their quiescence ( Hur et al., 2016 ). In light of the extensive literature, these findings have been particularly provocative, as this was the first description of ACKR1 expression by any leukocyte type and, if correct, would change current concepts of ACKR1 involvement in pathophysiology. The reported ACKR1 expression by macrophages in Hur et al. relied on using commercial anti-ACKR1 antibody FAB6695, which has neither been validated by the manufacturer nor by the authors. This prompted us to investigate the specificity of FAB6695 and scrutinize the apparent ACKR1 expression in BM macrophages" Read more at the source #DrGPCR #GPCR #IndustryNews

G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation

August 2022 "GPR21 is an orphan and constitutively active receptor belonging to the superfamily of G-Protein Coupled Receptors (GPCRs). GPR21 couples to the Gq family of G proteins and is expressed in macrophages. Studies of GPR21 knock-out mice indicated that GPR21 may be involved in promoting macrophage migration. The aim of this study was to evaluate the role of GPR21 in human macrophages, analyzing (i) its involvement in cell migration and cytokine release and (ii) the consequence of its pharmacological inhibition by using the inverse agonist GRA2. THP-1 cells were activated and differentiated into either M1 or M2 macrophages. GPR21 expression was evaluated at gene and protein level, the signalling pathway was investigated by an IP1 assay, and cytokine release by ELISA. Cell migration was detected by the Boyden chamber migration assay, performed on macrophages derived from both the THP-1 cell line and human peripheral blood monocytes." Read more at the source #DrGPCR #GPCR #IndustryNews

These results suggest that synaptamide/GPR110 signaling negatively regulates osteoclastogenesis.

August 2022 "Background and purpose: Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca2+ channels (VGCCs). Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, associate with elevated blood pressure; however, neither SVEP1 nor integrin α9β1 has reported roles in vasoregulation. We determined whether SVEP1 and integrin α9β1 can regulate VSMC contraction." Read more at the source #DrGPCR #GPCR #IndustryNews

Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation

October 2022 "Over three decades of research have provided thorough insights into G protein-coupled receptor (GPCR) regulation. In a recent issue of Molecular Cell, Fonseca et al. identified a previously overlooked desensitization mechanism. Agonist activation of the β2-adrenoceptor (β2AR) causes its S-nitrosylation that is required for the receptor to internalize and desensitize. Eliminating β2AR S-nitrosylation by mutation of C265 augments β2AR protein kinase A signaling, enables β2AR nitric oxide (NO) signaling, renders mice resistant to bronchoconstriction, and protects mice from allergen-induced asthma." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Aims: The pathophysiological mechanism(s) underlying non-alcoholic fatty liver disease (NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated receptor (PPAR) α/γ agonist saroglitazar, has been approved. Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent hepatic dysfunction. " Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Cannabinoid Receptor 2 (CB2) is a G protein-coupled receptor (GPCR) with considerable, though as yet unrealised, therapeutic potential. Promising preclinical data supports the applicability of CB2 activation in autoimmune and inflammatory diseases, pain, neurodegeneration, and osteoporosis. A diverse pharmacopoeia of cannabinoid ligands is available, which has led to considerable advancements in the understanding of CB2 function and extensive preclinical evaluation. However, until recently, most CB2 ligands were highly lipophilic and as such not optimal for clinical application due to unfavourable physicochemical properties. A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties and a few such compounds have now undergone clinical trial. We review the current state of CB2 ligand development and progress in optimising physicochemical properties, understanding advanced molecular pharmacology such as functional selectivity, and clinical evaluation of CB2-targeting compounds." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Cannabinoid Receptor 2 (CB2) is a G protein-coupled receptor (GPCR) with considerable, though as yet unrealized, therapeutic potential. Promising preclinical data support the applicability of CB2 activation in autoimmune and inflammatory diseases, pain, neurodegeneration, and osteoporosis. A diverse pharmacopeia of cannabinoid ligands is available, which has led to considerable advancements in the understanding of CB2 function and extensive preclinical evaluation. However, until recently, most CB2 ligands were highly lipophilic and as such, not optimal for clinical application due to unfavorable physicochemical properties. A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties and a few such compounds have now undergone clinical trials. We review the current state of CB2 ligand development and progress in optimizing physicochemical properties, understanding advanced molecular pharmacology such as functional selectivity, and clinical evaluation of CB2-targeting compounds." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 TAS2R supports odontoblastic differentiation of human dental pulp stem cells in the inflammatory microenvironment "Background: Inflammatory microenvironment promotes odontoblastic differentiation in human dental pulp stem cells (hDPSCs), but the regulatory mechanisms remain unclear. In this study, we aimed to explore the role of TAS2R in odontoblastic differentiation of hDPSCs in the inflammatory microenvironment. Methods: Microarray analysis was performed to explore the differential mRNA profiles in inflammatory and healthy pulp tissues from the patients. hDPSCs isolated from the healthy pulp tissues were stimulated by LPS, TNFα and IL-6, respectively, to verify the effect of TAS2R. The expression markers related to odontoblastic differentiation of hDPSCs were observed by qPCR and chemical staining methods. TAS2R10 was overexpressed or silenced to observe the effect on odontoblastic differentiation of hDPSCs under LPS stimulation. The G protein and intracellular Ca2+ were detected, respectively, by qPCR and Fluo-4AM Ca2+ fluorescent probe." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Ginsenoside Rg5 allosterically interacts with P2RY12 and ameliorates deep venous thrombosis by counteracting neutrophil NETosis and inflammatory response "Deep venous thrombosis (DVT) highly occurs in patients with severe COVID-19 and probably accounted for their high mortality. DVT formation is a time-dependent inflammatory process in which NETosis plays an important role. However, whether ginsenoside Rg5 from species of Panax genus could alleviate DVT and its underlying mechanism has not been elucidated." Read more at the source #DrGPCR #GPCR #IndustryNews

focuses on processes such as angiogenesis, cell signaling, stemness, metastasis, and drug resistance and inflammation

the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced inflammation GLP-1R to selectively restrain local and systemic T cell-induced, but not lipopolysaccharide-induced, inflammation activation in gut IELs to modulation of microbiota composition and control of intestinal and systemic inflammation

GPCRs in Cardiology, Endocrinology, and Taste FFAR4 regulates cardiac oxylipin balance to promote inflammation resolution in HFpEF secondary to metabolic syndrome.

fibrotic bone The orphan G protein-coupled receptor 141 expressed in myeloid cells functions as an inflammation discovery of G protein-coupled receptor-targeting biologics Lipid mediators in neutrophil biology: inflammation , resolution and beyond Exploring GPCR signaling pathway networks as cancer therapeutic targets Generation Effects of NBI-1117567 in Healthy Adults Crinetics Pharmaceuticals Reports First Quarter 2024 Financial Results and Provides Business Update Nxera Pharma Operational Highlights and Consolidated Results for the First

Using time-resolved cryo-electron microscopy (cryo-EM) and variability analysis to monitor the transitions transition structures generated from overlapping particle subsets along this pathway provide a high-resolution With this high-resolution, dynamic view of GPCR activation, scientists can better tackle diseases by Time-resolved cryo-EM of G-protein activation by a GPCR. Nature (2024).

(Nasdaq: CRNX), announced that results from the company’s Phase 1 study of CRN04894, the company’s investigational

novel medicines for patients with central nervous system (CNS) disorders, today reported its financial results

ligands CXCL9, CXCL10, and CXCL11 and enables the recruitment of immune cell subsets leading to damage of inflamed In a LPS-induced lung inflammation model in mice, ACT-660602 led to significantly reduced recruitment

A2A adenosine receptor (A2AAR) have been considered promising agents to treat Parkinson's disease, inflammation structures of 2 in complex with two thermostabilized A2AAR constructs were solved at 2.05 and 2.80 Å resolutions

modulation-based drug discovery and development, today reported its half-year and second quarter financial results

August 2022 Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-2 Trial of KarXT in medicines for people living with psychiatric and neurological conditions, today announced positive topline results