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Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor Induces Release of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling G protein-coupled receptors Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation

transcriptomics and peptidomics of central nervous system identify neuropeptides and their G protein-coupled receptors Neuropeptides and their specific receptors (primarily G protein-coupled receptors, GPCRs) regulate multiple

Recurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors expressed in tumors G protein-coupled receptors (GPCRs) are the largest family of human proteins. Because there are many more GPCRs than effectors, mutations in different receptors could perturb signaling but rather that cognate mutations with similar effects on GPCR function are distributed across many receptors We also discovered that no single receptor drives this pattern, but rather multiple receptors contain

September 2022 "GPCRs are the most potential targets for drug discovery, however, their role in oncology is underappreciated and GPCR-based anti-cancer drug is not fully investigated. Herein, we identified GPR108, a GPCR protein described in innate immune system, is a potential therapeutic target of cancer. Depletion of GPR108 dramatically inhibited the survival of various cancers. Notably, TNFα activation of NF-κB was totally impaired after GPR108 knockout. We identified gambogic acid (GA), a natural prenylated xanthone, selectively targeting GPR108. Importantly, GA engaged with GPR108 and promoted its degradation, knockout of GPR108 remarkably blocked GA inhibition of NF-κB signaling. Furthermore, in vitro and in vivo assays demonstrated that GA was dependent on GPR108 to exert anti-cancer activity. Overall, our findings supported GPR108 as a promising therapeutic target of cancer, and provided a small molecule inhibitor GA directly and selectively targeting GPR108 for cancer therapy." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "GPCR signaling and function depend on their associated proteins and subcellular locations. Besides G-proteins and β-arrestins, 14-3-3 proteins participate in GPCR trafficking and signaling, and they connect a large number of diverse proteins to form signaling networks. Multiple 14-3-3 isoforms exist, and a GPCR can differentially interact with different 14-3-3 isoforms in response to agonist treatment. We found that some agonist-induced GPCR/14-3-3 signal intensities can rapidly decrease. We confirmed that this phenomenon of rapidly decreasing agonist-induced GPCR/14-3-3 signal intensity could also be paralleled with GPCR/β-arrestin-2 signals, indicating diminished levels of GPCR/signal adaptor complexes during endocytosis. The temporal signals could implicate either GPCR/14-3-3 complex dissociation or the complex undergoing a degradation process. Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting a new approach for GPCR drug development by modulating GPCR/14-3-3 signals temporally." Read more at the source #DrGPCR #GPCR #IndustryNews

This facilitates the study of receptor dynamics, ligand binding and signaling in real time. offering optimized fluorescent ligands specifically designed for GPCR targets , including CELT-240 for hD2/D3 dopamine receptors and CELT-483 for the hσ1/σ2 sigma receptor. CELT-240 in flow cytometry binding assays is suitable to measure the affinity of compounds for the D2/D3 receptors.

it contributes to pathophysiology, which is likely due to complex interactions among neuropeptides, receptor

This communication involves the ligand-mediated control of cell surface receptors that then direct their has been placed on the ability of these therapeutics to modulate diseases by acting at cell surface receptors GPCR superstructures, termed receptorsomes, both at the cell surface membrane and in the intracellular domain

validation of recombinant protein standards for quantitative Western blot analysis of cannabinoid CB1 receptor assays with antibody-antigen interaction-based approaches for quantitative analysis of G protein-coupled receptor GPCRs in general and cannabinoid CB1 receptor in particular show a progressive tendency to aggregate context due to the low solubility that the hydrophobic nature imprinted by their seven transmembrane domains Estimated values of CB1 receptor density obtained by quantitative Western blot were of the same order

advent of AlphaFold, homology modeling was the most common method for predicting G protein-coupled receptor cellular environment which are crucial for understanding how drugs can selectively target different receptor To fully understand GPCR behavior and optimize drug targeting across multiple receptor states, experimental Ligand discovery from a dopamine D3 receptor homology model and crystal structure. AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor

This makes them very useful for GPCR drug discovery, since receptors are a lot bigger than their small where they used CELT-419 for D3 dopamine receptor binding assays in baculoviruses. 3.       extended periods (at least 60 to 90minutes), being limited by the stability of the fluorescent ligand or receptor and protein matters (for the rotation to be slowed), not the distance between the protein, donor and acceptor

GPCR contributor article Canonical chemokine receptors as scavenging “decoys” Shivani Sachdev, Brendan Bouvier, Jana Selent, et al. for their study on G protein-specific mechanisms in the serotonin 5-HT2A receptor function, impacting synaptic transmission Orphan receptor GPR88 as a potential therapeutic target for PC12 cells 17-β-estradiol potentiates the neurotrophic and neuroprotective effects mediated by the dopamine D3/acetylcholine nicotinic receptor heteromer in dopaminergic neurons A new GRAB sensor reveals differences

CXV: The Class F of G Protein-Coupled Receptors Yusman Manchanda, Dr. the therapeutic prospects of EGFR inhibition in rotenone-mediated parkinsonism in rats: Modulation of dopamine D3 receptor Molecular insights into orphan G protein-coupled receptors relevant to schizophrenia Single Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics Reviews, GPCRs CXV: The Class F of G Protein-Coupled Receptors Structural and Molecular Insights into GPCR Function

spectroscopy to characterize ligand interactions with cell surface membrane proteins such as G-protein coupled receptors (GPCRs) and receptor tyrosine kinases. delineation of ligands involved in binding, ligand bound-state conformational determination, evaluation of receptor structuring and dynamics, and inference of distance constraints characteristic of the ligand-receptor

October 2022 "Background: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen intake by the electron transport chain from ATP production in the inner membrane of the mitochondria. The physiological activities of UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis and progression of diabetes mellitus is among the greatest concerns. UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting diabetes mellitus patients who are experiencing oxidative stress. Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through protein uncoupling." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "The activity of dopamine neurons is dependent on both intrinsic properties and afferent , D2 and GABAB receptors. Each of these receptors activates G protein-coupled inwardly rectifying potassium (GIRK) channels. KEY POINTS: Inhibitory D2 and GABAB receptors modulate dopamine neuron activity through shared G protein-coupled in the context of other G protein-coupled receptors."

August 2022 "The apelin receptor (APJ) is a target for cardiovascular indications.

Celtarys Research expands its assay tools with CELT-419 for D3 receptor studies, and Dr. Terry Kenakin brings translational clarity to complex receptor concepts.   Platforms   Celtarys Research presents CELT-419, a nanomolar-affinity fluorescent ligand optimized for D3 receptor assays in both baculovirus and live-cell systems. Highlights     Phosphorylation selectively regulates β-arrestin recruitment  across glucagon family receptors

GPCRs in Cardiology, Endocrinology, and Taste G-protein coupled receptor 19 (GPR19) knockout mice display Neurotensin receptor 1-biased ligand attenuates neurotensin-mediated excitation of ventral tegmental area dopamine neurons and dopamine release in the nucleus accumbens. Methods & Updates in GPCR Research Activity Map and Transition Pathways of G Protein-Coupled Receptor Computational insights into ligand-induced G protein and β-arrestin signaling of the dopamine D1 receptor

GPCR Activation and Signaling Coupling between GPR143 and dopamine D2 receptor is required for selective potentiation of dopamine D2 receptor function by L-3,4-dihydroxyphenylalanine in the dorsal striatum Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling GPCR Binders Gαi-derived peptide binds the µ-opioid receptor. A growing understanding of the role of muscarinic receptors in the molecular pathology and treatment

critical components of the intracellular signaling pathways that mediate the effects of G protein-coupled receptors selective for certain GPCRs, as a proof RGS4 which is expressed in the brain, has been shown to modulate dopamine signaling by specifically regulating the activity of the dopamine D2 receptor; enhancing the activity of the G protein that is coupled to the receptor and leading to a decrease in dopamine signaling[4, Zhuang, Y., et al., Structural insights into the human D1 and D2 dopamine receptor signaling complexes

  📚 This week’s paper highlights: GLP-1R/GIPR biased agonism enhances metabolic outcomes Ghrelin receptor Constitutive ghrelin receptor activity, not dimerization or ligand binding —reverses dopamine D2 signaling

activation dynamics, ligand binding geometry and receptor interactions.   all kinds of dyes, such as pharmacophores conjugated to near-infrared fluorophores ( CELT-075 hD2 dopamine receptor fluorescent antagonist and CELT-095 hM1/M2 muscarinic receptor fluorescent antagonist). What are the current trends in G protein-coupled receptor targeted drug discovery? Portraying G protein-coupled receptors with fluorescent ligands.

, Joshua Levitz for their work on Emerging modes of regulation of neuromodulatory G protein-coupled receptors GPCR Activation and Signaling Emerging modes of regulation of neuromodulatory G protein-coupled receptors synaptic glutamate time course at hippocampal CA1 synapses Regulator of G protein signaling 6 (RGS6) in dopamine adult male mice Methods & Updates in GPCR Research RNA therapeutics in targeting G protein-coupled receptors Pharmacology 2026 GPCR Jobs HIGHLIGHT Principal Scientist, In vitro pharmacology Senior Scientist - Receptor

Adhesion GPCRs Amelioration of non-alcoholic fatty liver disease by targeting adhesion G protein-coupled receptor of the glucagon receptor is dynamic Ligand recognition and G protein coupling of the human itch receptor 1-biased ligand attenuates neurotensin-mediated excitation of ventral tegmental area dopamine neurons and dopamine release in the nucleus accumbens Understanding the Molecular Regulation of Serotonin Receptor Insights into GPCR Function A method for structure determination of GPCRs in various states Apelin receptor

Janicot , and Mikel Garcia-Marcos for their excellent work on Protocol to investigate G protein-coupled receptor constitutive activation and CXCL1 chemokine recognition Structural basis of psychedelic LSD recognition at dopamine D1 receptor Structural basis of μ-opioid receptor targeting by a nanobody antagonist Probing the energy landscape of the lipid interactions of the serotonin1A receptor Potential allosteric pockets identification of glucagon receptor based on molecular dynamics simulations Leukotriene B4 receptor 1 (BLT1) activation

Can we leverage structural and computational insights not just to explain receptor–ligand interactions challenge  such as differentiating agonists from antagonists, predicting biased agonism, or achieving receptor Instead of rehashing how a known ligand binds to a known receptor, they aim to produce predictions that For dopamine receptor studies, they built predictive models before experimental structures were available It struggles with ligand-bound conformations, GPCR–G protein complexes, and receptor–peptide interactions

includes congrats to: Junyi Liang, Niña Caculitan, and Adam W Smith for their research on β2-adrenergic receptor restoration of tension in epithelial cells Profiling the proximal proteome of the activated μ-opioid receptor the therapeutic prospects of EGFR inhibition in rotenone-mediated parkinsonism in rats: Modulation of dopamine D3 receptor Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and in human cancer cells [Inhibitory effect of downregulating G protein-coupled receptor class C group

Di Pizio, Jiafei Mao, Jana Selent, et al. for their research on the Relevance of GPCR dynamics for receptor to heterotrimeric G protein activity biosensors Descriptive molecular pharmacology of the δ opioid receptor complex in promoting G protein translocation to endosomes GPCRs in Neuroscience An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake The for receptor activation, signalling bias and allosteric modulation Structural and Molecular Insights

This Week’s Highlights: G protein-coupled receptor (GPCR) pharmacogenomics Miles D Thompson , David internalization in CXCR1 signalling GPCR Binders, Drugs, and more G protein-coupled receptor (GPCR) Therapy GPCRs in Neuroscience Innervation density governs crosstalk of GPCR-based norepinephrine and dopamine -1 IgG Autoantibodies in Patients with COVID-19 Signaling by neutrophil G protein-coupled receptors that kinases The membrane domains of mammalian adenylyl cyclases are lipid receptors Structural insights