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August 2022 A NanoBRET-Based H 3 R Conformational Biosensor to Study Real-Time H 3 Receptor Pharmacology Membranes and Living Cells "Conformational biosensors to monitor the activation state of G protein-coupled receptors addition to the molecular pharmacology assay toolbox to characterize ligand efficacy at the level of receptor We recently reported the initial characterization of a NanoBRET-based conformational histamine H3 receptor

August 2022 G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation "G protein-coupled receptor kinase type 2 (GRK2) and β-arrestin2 are representative proteins that regulate the transduction and trafficking of G protein-coupled receptor (GPCR) signaling

In particular, CBD is able to modulate different receptors in the endocannabinoid system, some of which belong to the family of G-protein-coupled receptors (GPCRs). 55 (GPR55) and the cannabinoid type 1 receptor (CB1). addition, our results suggest a previously unknown sodium-binding site located in the extracellular domain of the CB1 receptor.

Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of a great variety

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors

How the Mass Action Law underpins nearly every model Future of Receptor Theory: Linkage vs.

G protein-coupled receptor kinase 2 is essential to enable vasoconstrictor-mediated arterial smooth muscle circulation of vasoconstrictors, resulting in enhanced signalling through their cognate G protein-coupled receptors In VSMC, G protein-coupled receptor kinase 2 (GRK2) is known to regulate numerous vasoconstrictor GPCRs

The mouse cytomegalovirus G protein-coupled receptor homolog, M33, coordinates key features of in vivo repertoire Common to all cytomegalovirus (CMV) genomes analysed to date is the presence of G protein-coupled receptors IMPORTANCE G protein-coupled receptors (GPCRs) act as cell surface molecular "switches" which regulate

proteomes, we identified lysosomal cholesterol signaling (LYCHOS, previously annotated as G protein-coupled receptor

September 2022 Isoforms of GPR35 have distinct extracellular N-termini that allosterically modify receptor-transducer coupling and mediate intracellular pathway bias "Within the intestine, the human G protein-coupled receptor activation and signaling of 10 different heterotrimeric G proteins, ligand-induced arrestin recruitment, and receptor results reveal that the extended N-terminus of the long isoform limits G protein activation yet elevates receptor-β-arrestin contributed by the extended N-terminus of the long GPR35 isoform limits the extent of agonist-induced receptor-β-arrestin2

Phenylalanine 193 in Extracellular Loop 2 of the β 2-Adrenergic Receptor Coordinates β-Arrestin Interaction G protein-coupled receptors (GPCRs) transduce a diverse variety of extracellular stimuli into intracellular These receptors are the most clinically productive drug targets at present. components of receptor-effector interactions remain incompletely described. SIGNIFICANCE STATEMENT: The role of extracellular G protein-coupled receptor (GPCR) domains in mediating

conditions, what appears to be a second high-affinity site may simply reflect kinetic factors—such as ligand-receptor-G

on the mechanism of signal activation, ligand selectivity and allosteric modulation in angiotensin receptors Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. Recently, X-ray structures of both AngII receptors (AT1 and AT2 receptors) bound to peptide and non-peptide , as the basis of ligand selectivity, efficacy, and regulation of the molecular functions of the receptors This review covers the new data elucidating the structural dynamics of AngII receptors and how structural

, essential to maintaining proper cardiac output and circulation, is regulated by G protein-coupled receptor

2022 N-terminal alterations turn the gut hormone GLP-2 into an antagonist with gradual loss of GLP-2 receptor selectivity towards more GLP-1 receptor interaction "Background and purpose: To fully elucidate the regulatory role of the GLP-2 system in the gut and the bones, potent and selective GLP-2 receptor (GLP To examine selectivity, COS-7 cells expressing human GLP-1 or GIP receptors were assessed for cAMP accumulation

pro-inflammatory neutrophil response, signaling downstream of an agonist-activated G protein-coupled receptor Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination The medium chain fatty acid receptor GPR84 as well as formyl peptide receptor 2 (FPR2), receptors expressed

Reflex arcs, compensatory pathways, and receptor trafficking can turn your expected outcome on its head red flags early and make course corrections before trials derail. ✅ Practical strategies  for using receptor Dobutamine’s dual action on beta and alpha receptors, for example, invites reflex bradycardia that blunts Internalized Signaling: Same Receptor, Different Story A GPCR response isn’t always over when the receptor In this module, you’ll explore how some receptor–agonist complexes continue signaling from endosomes,

Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals

Watch Episode 172 What happens when the career you planned no longer feels right? For Catherine Demery, it meant rewriting everything on her own terms. She entered undergrad set on becoming a pharmacist. After excelling in the PCAT and gaining admission to pharmacy school at the University of Michigan, it seemed like her path was locked in. But something shifted. “I kind of had an identity crisis because I think I realized in that moment that I didn't want to be a pharmacist but I had tailored four years of my life to doing so." Two weeks before orientation, Catherine deferred her acceptance. It was a bold, uncertain move—but one that became the catalyst for a new trajectory. She found herself drawn toward the science behind the drugs, rather than their clinical application. That insight eventually led her into industry. Learning the Lab, Learning Herself During her time at the contract research organization (CRO) in Ann Arbor, Catherine was immersed in analytical work under stringent GLP/GMP standards. It was here that the disciplined structure of industry science helped her re-find purpose and build confidence for what came next. “This wasn’t with much foresight for a couple years down the road. It was mostly just because, I need to be back in the lab.” In that environment, every project brought new challenges—deadlines, documentation, and deliverables for paying clients. Catherine’s methodical retention of those skills later gave her a solid foundation in her academic work, even when expectations were looser in academia. The Spark of Addiction Science After two years in industry, Catherine enrolled in a master’s program in pharmacogenomics at Manchester University. There, she chose to write a review on genetic variation in susceptibility to alcoholism and opioid addiction—a decision that would reshape her academic ambitions. “...I had a light bulb moment where I felt for the first time in my life, I understood why people pursued a PhD. I was staying up super late. I was excited to work on this, till 2 or 3 a.m.” That project was her lightbulb moment. She finally understood what it meant to be driven by a research question, not just assigned to one. For the first time, she saw herself as a future researcher, not just a technician or a student. A Detour Through Immunology Her growing interest in addiction led her to the NIH’s Perinatology Research Branch in Detroit. While her work there focused on immunological changes in pregnancy—not addiction—it was a valuable chapter. She gained exposure to in vivo models, immunology, and complex study design, while also getting closer to patient-centered research. “It really forced me to kind of patch up all my immunology holes and then apply them. I came away from that job with just a whole new appreciation for immunology and for pregnancy. It was really, really fascinating… and just eye opening to a part of the world that I don’t think I would have put that much thought into ever again.” This experience sharpened her conceptual range and prepared her for the next step. Returning to the Opioid Questions That Mattered Now, as a PhD candidate in the Traynor and Anand labs at the University of Michigan, Catherine is focused on the mechanisms of opioid-induced respiratory depression, particularly involving fentanyl and xylazine. Her current work examines how these substances, when used alone or together, impair breathing in mice. She uses whole-body plethysmography and pulse oximetry to dissect the specific ways these drugs impact the respiratory cycle. It’s rigorous pharmacology, but deeply tied to urgent public health needs. And it’s also deeply personal. "I've always been really passionate and somewhat sensitive to people who struggle with opioid abuse. I had a few friends who became addicted and, really sadly, many of whom actually passed away as a result of an overdose. And so, that certainly shaped my interests and passions as a scientist." What Can You Learn from Catherine’s Story? A career pivot is not a failure—it’s a refined strategy. Industry can build skills that academia often overlooks. Your passion might not come first—it might come from doing the work. The most impactful science is often personal. Technical discipline is transferable—even across research cultures. The Importance of Passion in Research Catherine's journey highlights the importance of passion in research. It is not just about following a predetermined path; it is about discovering what truly drives you. Passion can lead to groundbreaking discoveries and a fulfilling career. When you find something that excites you, it can transform your work into a source of joy and motivation. Catherine's experience serves as a reminder that it is never too late to change direction and pursue what you love. Embracing Change and Uncertainty Change can be daunting, especially when it involves stepping away from a well-defined career path. However, embracing uncertainty can lead to unexpected opportunities. Catherine's decision to defer pharmacy school was a leap of faith that opened new doors. In life and career, taking risks can lead to personal and professional growth. It is essential to remain open to new experiences and to trust your instincts. This mindset can lead to a more fulfilling and successful career. Conclusion: A Journey of Self-Discovery Catherine Demery's story is one of self-discovery and resilience. It shows that career paths can evolve, and that it is possible to find fulfillment in unexpected places. Her journey illustrates the power of following one's passion and the importance of being adaptable in the face of change. In the end, it is about finding what resonates with you and pursuing it wholeheartedly. Catherine's experience serves as an inspiration for anyone considering a career change or seeking to align their work with their passions. _______ Keyword Cloud : #XylazineResearch #OpioidPharmacology #muOpioidReceptor #RespiratoryDepression #AddictionScience #DrGPCRecosystem #FentanylOverdose

Previously, we identified potent positive crosstalk between insulin/IGF-1 receptors and G protein-coupled

Rho1 signaling is activated by G-protein-coupled receptor (GPCR) signaling at the cell surface. The SG receptor that transduces the Fog signal into Rho1-dependent myosin activation has not been identified

September 2022 Microbial Metabolites Orchestrate a Distinct Multi-Tiered Regulatory Network in the Intestinal Epithelium That Directs P-Glycoprotein Expression "P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal role in removal of toxins and efflux of endocannabinoids to prevent excessive inflammation and sustain homeostasis. Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp expression. We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp. RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp induction. Using shRNA knockdown and CRISPR/Cas9 knockout cell lines, as well as mouse models, we confirmed the RNA sequencing findings and discovered a role for intestinal HNF4α in P-gp regulation. These findings shed light on a sophisticated signaling network directed by intestinal microbial metabolites that orchestrate P-gp expression and highlight unappreciated connections between multiple pathways linked to colonic health." Read more at the source #DrGPCR #GPCR #IndustryNews

The real friction point lies downstream : translating receptor–ligand interactions into actionable development Antibodies, Bias, and the Expanding Modality Landscape Antibody therapeutics are now entering spaces once dominated

Unlocking the Puzzle: The Importance of Precision in GPCR Programs and the Hidden Costs of Overlooking Details. A GPCR program can have world-class science, top-tier talent, and millions in funding — and still fail. Not because the science is wrong. Not because the people aren’t brilliant. But because the program is run on duct tape and heroics instead of precision. Your program isn’t slipping because of bad science — it’s bleeding money because your systems were broken before the first experiment ran. And every time your Head of Biology spends each night copy-pasting data instead of thinking about the next experiment, your program is bleeding six figures in lost time and wasted salaries. Brilliant minds doing low impact work is not a strategy. It’s a slow-motion car crash. Hiring Won’t Save Your GPCR Drug Discovery Program When a drug discovery program stalls, the default reflex is always the same: hire more people. Bring in a computational chemist. Add a data scientist. Surely more hands will move the needle. But here’s the reality: even ultra-specialized experts can’t fix systemic dysfunction in their spare time. They’re hired for science, not for building operational scaffolding. And when you chain your highest-paid scientists to repetitive admin work, you’re not solving problems — you’re multiplying them. Every two-week delay in a DMTA cycle can burn through hundreds of thousands in salaries and overhead. That’s not a hiccup. That’s a hemorrhage. Bad Data Management Is Undermining Your GPCR Drug Discovery Team The real problem isn’t competence. It’s the absence of operational precision. Even flawless experiments collapse under sloppy systems. A few familiar failure points: Fragmented Data: GPCR programs spew data across files, folders, and inboxes. Without a unified drug discovery data management  pipeline, teams waste hours cleaning, reconciling, and integrating before they can even think about analysis. A good ELN that pipes instrument outputs into a central hub — where QC, analysis, consumption and consolidation across assays — isn’t a luxury. It’s oxygen. Undefined Protocols: “We’ll figure it out” is not a workflow. Without clear rules of engagement, communication becomes chaos, progress gets lost in Slack threads, and insights die in inboxes. Ambiguous Decision Gates: Molecules advance or stall based on vibes, not criteria. That leads to premature investment in weak scaffolds or endless tinkering with dead ends. These aren’t minor oversights. They’re cracks in the foundation. And cracks don’t stay small for long. Build Precision Systems for GPCR Drug Discovery The only way out for GPCR drug discovery programs isn’t more people or shinier assays. It’s a deliberate blueprint for precision. This doesn’t mean an overnight overhaul. It means a commitment to continuous improvement — starting with the highest-friction gaps and working upward. Plan, fix at the root, and stop fighting the same fire every week. The payoff? Progress that’s predictable, not reactive. The Hidden Costs of Poor Drug Discovery Data Management Stop pretending more hires or new assays will save you. They won’t. Every DMTA cycle lost to fragmented data and sloppy processes costs your company hundreds of thousands of dollars. That’s not “part of the process.” That’s a chaos tax — and you’re paying it in cash, time, and morale. If you want your program to survive, you need a Blueprint for Precision. Not next quarter. Not after the next fire drill. Now. Because the truth is harsh: in drug discovery, you don’t run out of science. You run out of money. And if your systems aren’t built for precision, you’ll run out fast. 👉 In Part 2, we’ll expose exactly how fragmented data cripples GPCR programs — and how to fix it before it sinks yours. And if you’re already seeing the cracks? Don’t wait for Part 2. Reach out. Let’s build the systems now, before the next delay burns another half a million. 🚀 Book your free 30-minute precision audit — before your next DMTA cycle costs another $200K Let’s unlock the momentum your GPCR program needs. 👉 https://calendly.com/drgpcr/yamina-corner Or explore how we can work together: 👉   Yamina.org

Excited to hear Dr. Sandra Berndt talk about new structural perspectives in GPCR-mediated Src family kinase activation. Register here (FREE) https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe #drgpcr #gpcr #virtualcafe

CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal Stability to the Serotonin 1A Receptor "G protein-coupled receptors (GPCRs) constitute the largest class of membrane proteins that transduce The serotonin1A receptor is a crucial neurotransmitter receptor in the GPCR family involved in a multitude In addition, we showed that membrane cholesterol stabilizes the serotonin1A receptor against thermal consensus (CRAC) motif in transmembrane helix 2 in conferring the thermal stability of the serotonin1A receptor

Consider G-protein-coupled receptors-an expansive class of transmembrane signaling proteins that participate While early evidence for the role of oligomerization in receptor signaling came from ensemble biochemical for these techniques to advance our understanding of the role of oligomerization in G-protein-coupled receptor

August 2022 "Emerging evidence suggests that G protein-coupled receptor (GPCR) kinases (GRKs) are associated Further molecular dynamics simulation studies reveal an interaction between the βarr2 finger loop domain

October 2022 "Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal domain. Interestingly, unlike PAR2-AP, GB83 and trypsin induced sustained receptor endocytosis and PAR2 colocalization

What if you could directly measure receptor internalization in physiologically relevant cells without These probes become brighter and have a longer lifespan as internalized receptors enter acidic endosomes—translating his team presented a data set that transformed everything: a clean, dose-dependent response of GLP-1 receptor