Obesity-induced changes in human islet G protein-coupled receptor expression: Implications for metabolic regulation G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that are the targets for many different classes of pharmacotherapy. The islets of Langerhans are central to appropriate glucose homeostasis through their secretion of insulin, and islet function can be modified by ligands acting at the large number of GPCRs that islets express. The human islet GPCRome is not a static entity, but one that is altered under pathophysiological conditions and, in this review, we have compared expression of GPCR mRNAs in human islets obtained from normal weight range donors, and those with a weight range classified as obese. We have also considered the likely outcomes on islet function that the altered GPCR expression status confers and the possible impact that adipokines, secreted from expanded fat depots, could have at those GPCRs showing altered expression in obesity. Read full article

chemokines and growth factors, which upon release may directly engage pathogens and/or contribute to inflammatory interplay between platelets and NETs and the potential of this alliance to influence the course of inflammatory

September 2022 GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome The fact that GPR84 expression in leukocytes is remarkably increased under acute inflammatory stimuli Here we demonstrate that GPR84 is highly upregulated in inflamed colon tissues of active ulcerative colitis GPR84 activation imposes pro-inflammatory properties in colonic macrophages through enhancing NLRP3 inflammasome These results define a unique role of GPR84 in innate immune cells and intestinal inflammation, and suggest

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 Trehalose is a disaccharide sugar with known pro‐autophagy activity and effective in alleviating diverse inflammatory The mechanisms underlying their anti‐inflammatory effects were assessed using specific inhibitor, genetic

September 2022 Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following -7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory

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

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

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

G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation roles in the pathological mechanisms of a wide range of diseases including heart failure, cancer, and inflammatory in immune cell function and focuses on the pathological implications of GRK2/β-arrestin2 in various inflammatory

August 2022 TAS2R supports odontoblastic differentiation of human dental pulp stem cells in the inflammatory microenvironment " Background: Inflammatory microenvironment promotes odontoblastic differentiation this study, we aimed to explore the role of TAS2R in odontoblastic differentiation of hDPSCs in the inflammatory Methods: Microarray analysis was performed to explore the differential mRNA profiles in inflammatory

August 2022 "Bone remodeling is precisely regulated mainly by osteoblasts and osteoclasts. Although some G-protein coupled receptors (GPCRs) were reported to play roles in osteoblast function, little is known about the roles in osteoclasts. In this study, we found, for the first time, that the expression of GPR110 increased during osteoclastogenesis. GPR110 belongs to adhesion GPCR and was the functional receptor of N-docosahexaenoyl ethanolamine (also called synaptamide). Synaptamide suppressed osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand. Considering that synaptamide is the endogenous metabolite of DHA, we hypothesized that DHA may inhibit osteoclastogenesis by affecting synaptamide/GPR110 signaling. But GPR110 knockout and subsequent rescue experiments revealed a pivotal role of GPR110 in the attenuation of osteoclastogenesis by synaptamide but not by DHA. These results suggest that synaptamide/GPR110 signaling negatively regulates osteoclastogenesis. Our study suggested that ligands of GPR110, such as synaptamide, might be a useful drug for osteoporotic patients." Read more at the source #DrGPCR #GPCR #IndustryNews

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

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

Promising preclinical data supports the applicability of CB2 activation in autoimmune and inflammatory

Promising preclinical data support the applicability of CB2 activation in autoimmune and inflammatory

interacts with P2RY12 and ameliorates deep venous thrombosis by counteracting neutrophil NETosis and inflammatory DVT formation is a time-dependent inflammatory process in which NETosis plays an important role.

Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation

receptor potential ankyrin subtype 1 protein (TRPA1) signaling pathways, thereby regulating proliferation, inflammation distributed in the brain, lung, heart, liver, spleen, pancreas, kidney, stomach, jejunum, ileum, colon, brown adipose tissue (BAT), white adipose tissue (WAT), and skeletal muscle.

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 Moreover, independent of glucose control or weight loss, the anti-inflammatory actions of GLP-1RAs require 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

efferent signals that link specific neural cell populations to the regulation of metabolic processes in adipose

August 2022 "Abstract The β3 -adrenergic receptor (β3 -AR) is found in several tissues such as adipose

the effects of RH on metabolic pathways associated with glucose counterregulation within liver, white adipose

MSCs have several sources and they can be derived from the umbilical cord, adipose tissue, and bone marrow

Alterations in mouse visceral adipose tissue mRNA expression of islet G-protein-coupled receptor ligands Targeted inhibition of the GRK2/HIF-1α pathway is an effective strategy to alleviate synovial hypoxia and inflammation

An allosteric modulator of the adenosine A1 receptor potentiates the antilipolytic effect in rat adipose

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