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disease (NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated receptor Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent

"Protecting neurons from death during oxidative and neuroexcitotoxic stress is key for preventing cognitive involving interaction between neurotrophic factor-α1 (NF-α1/carboxypeptidase E, CPE) and human 5-HTR1E, a G protein-coupled serotonin receptor with no previously known neurological function. cells with NF-α1/CPE increased pERK 1/2 and pCREB levels which prevented a decrease in pro-survival protein Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB

September 2022 "Introduction Protease activated receptors 1 (PAR1) and 4 (PAR4) agonists are used to C1-inhibitor (C1INH) is a protease inhibitor present in plasma but not in isolated platelet suspensions

Receptor access was unpredictable. Tissue responses defied the model. in living tissue — in a way that made receptor location and accessibility visible. and brain Being able to see receptor distribution is not just aesthetic — it shifts interpretation. For metabolic GPCRs (like GLP-1 and GIP receptors): Drug efficacy depends on which cells express the receptor Side effects are tied to where agonists bind Weight-loss and appetite effects often originate

September 2022 "Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid receptor To validate these processes, we employed GIRK4S143T, a MOR-activated Gβγ-protein effector, in combination

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, A major pan-receptor focus has been to identify GPCR-selective ligands that have bias in G protein-dependent the past two decades, it is only recently that highly β-arrestin biased ligands for the dopamine D1 receptor

We find that PFC astrocytes express receptors for dopamine but are unresponsive through the Gs/Gi-cAMP calcium signals in PFC astrocytes are time locked to dopamine release and are mediated by α1-adrenergic receptors active players in dopaminergic signaling in the PFC, contributing to PFC function though neuromodulator receptor

September 2022 Expression pattern and clinical significance of beta 2-adrenergic receptor in oral squamous carcinoma: an emerging prognostic indicator and future therapeutic target "Purpose: Beta 2-Adrenergic Receptor Immunohistochemistry, western blot and quantitative real-time PCR techniques were used to analyze β2-AR protein

Watch Episode 171 What happens when your protein has no known ligands, no structure, and very little The Problem: Hundreds of Receptors, Almost No Ligands Alessandro’s work focuses on olfactory GPCRs—nearly 400 distinct receptors that play key roles in smell but remain largely uncharacterized . Enter AlphaFold: Predicting the “Face” of a Receptor When Alessandro began his PhD, structural models The main challenge was simple but daunting: “The challenge was to get a face to those proteins—the structure

why two drugs with similar affinity may behave completely differently , and how the secret lies in receptor In this session, you’ll gain: ✅ A deeper understanding of how every ligand alters receptor conformation—and Ligands don’t just “bind”—they change  the receptor. These changes can alter how the receptor talks to G proteins, arrestins, or other receptors. receptors, where ligand context fundamentally changes modulator behavior.

Receptor density, constitutive activity, coupling efficiency, local signaling architecture, and physiological This is a core GPCR pharmacology insight:ligand → receptor → G protein is never the entire story. High-coupled systems inflate apparent efficacy; low-coupled systems expose its limits. Dr. expression and coupling efficiency. Interrogate agonists across multiple receptor-expression states.

November 2022 "Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various physiologies

September 2022 To probe the activation mechanism of the Delta opioid receptor by an agonist ADL5859 started from inactive conformation using molecular dynamic simulations "The δ-opioid receptor (DOR) is a critical While the receptor with the crystal ligand (i.e. antagonist naltrindole) maintained the inactive conformation in all three independent simulations, the receptor with ADL5859 was adopting toward the active conformation

regulation of cancer cell cycle and metastasis "β-Arrestins are ubiquitously expressed intracellular proteins identified for their contribution to GPCR desensitization to agonist-mediated activation, followed by receptor now recognized that in addition to GPCR arresting (hence the name arrestin). β-Arrestins are adaptor proteins recruitment, activation, and scaffolding of numerous cytoplasmic signaling complexes and assist in G-protein receptor signaling, thus bringing them into close proximity.

Breakthroughs this week: Structure-based discovery of positive allosteric modulators of the A1 adenosine receptor Principal Scientist - In Vitro Pharmacology; Senior Scientist, Molecular Pharmacology; PhD position in proteomics His work challenges outdated targets, explores overlooked roles of GPCRs and RGS proteins in pain, and Explore blind spots:  The underestimated role of GPCRs and RGS proteins in chronic pain mechanisms.

The company’s scientific approach relied on targeting GPCRs — specifically opioid receptors — using biased The company’s goal is to model receptor dynamics — including biased signaling — to predict drug behavior Superluminal is building systems that learn from receptor movement, conformational shifts, and complex protein-protein interactions.  By making receptor behavior computationally predictable, Ajay and his team are working to reduce the

September 2022 Cannabinoid type-2 receptors: An emerging target for regulating schizophrenia-relevant brain circuits "Although the cannabinoid type-2 receptor (CB2) is highly expressed in the immune system Recent anatomical studies, combined with electrophysiological studies, indicate that CB2 receptors are effects of CB2 receptor activation, make this receptor an intriguing target for treating schizophrenia , has greatly advanced our understanding of this receptor.

Jude; Postdoctoral Fellow at University of Copenhagen; PhD in proteomics and GPCR signaling in cancer conditions, what appears to be a second high-affinity site may simply reflect kinetic factors—such as ligand-receptor-G protein complex formation—creating the illusion of multiple sites that aren’t physiologically relevant

August 2022 "Abstract Sigma receptor is a transmembrane non-GPCR protein expressed mainly in the endoplasmic

September 2022 A2B Adenosine Receptor Enhances Chemoresistance of Glioblastoma Stem-Like Cells under Transcript and protein levels were determined by RT-qPCR and Western blot, respectively. we show for the first time that MRP3 expression is induced under hypoxia through the A2B adenosine receptor Downregulation of the A2B receptor decreases MRP3 expression and chemosensibilizes GSCs treated with These data suggest that hypoxia-dependent activation of A2B adenosine receptor promotes survival of GSCs

September 2022 Sweet taste receptor agonists attenuate macrophage IL‐1β expression and eosinophilic inflammation were assessed using specific inhibitor, genetic knockdown or knockout, and overexpression of cognate receptors

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

of the adhesion GPCR ADGRG6/GPR126 is a key regulator of receptor signaling Jiankun Lyu, Brian Shoichet GPCR Activation and Signaling Constitutive internalisation of EP2 differentially regulates G protein proteins Identification of Gα12-vs-Gα13-coupling determinants and development of a Gα12/13-coupled designer modulator Structural Insights into Partial Activation of the Prototypic G Protein-Coupled Adenosine G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 October 2024 | Biologics

September 2022 Lack of Oestrogen Receptor Expression in Breast Cancer Cells Does Not Correlate with Kisspeptin Signalling and Migration "Kisspeptin is an anti-metastatic mediator in many cancer types, acting through its receptor been associated with increased invasion and MMP-9 expression, leading to the suggestion that hormone receptor veracity of this claim, we compared endogenous KISS1R signalling and physiological output in the hormone receptor-negative

Drug discovery often assumes receptor inhibition follows simple rules—agonist binds, antagonist blocks Ways Schild plots reveal hidden complexities like allosterism and receptor heterogeneity. No reduction  in the maximal response (the receptor can still be fully activated). Curvature  can signify heterogeneous receptors  or mixed response mechanisms. In practice, a deviation in slope or curvature isn’t noise—it’s the receptor speaking.

Pharmacology isn’t only about ligands, receptors, and downstream G protein signaling—it’s also about Why System Sensitivity Matters Consider the signaling cascade: ligand binds receptor, receptor couples to G protein, G protein initiates downstream events. quantitative strength of this cascade depends not just on the ligand, but also on the abundance and coupling efficiency of the receptor system .

August 2022 "The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an

Upon activation, chemokine receptors coupe to the Gαi class of heterotrimeric G proteins, which, in turn receptors (ACKRs) which do not couple to G proteins and behave as scavenging “decoys” in order to either protein–coupled chemokine receptors that bind to the same ligand(s) (R. C terminus by G protein receptor kinases (GRKs), specifically GRK2 and GRK3 (A. Removal of G proteins by using CRISPR KO of Gαi (Gαi KO) or KO of all Gα subtypes (Gα_all KO) (M.

If the experiment is done on live cells , tracking real-time receptor internalization becomes possible Jang W, Senarath K, Feinberg G, Lu S, Lambert NA. Visualization of endogenous G proteins on endosomes and other organelles. eLife. 2024 Nov 8; 13:RP97033 Navarro G, Sotelo E, Raïch I, Loza MI, Brea J, Majellaro M. A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery.