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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

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.

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

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 .

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

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

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.

“This wasn’t with much foresight for a couple years down the road.

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.

exist in at least two distinct states: an active state characterized by high affinity for agonists when coupled to G proteins, and an inactive state in which their affinity for agonists diminishes in the absence of G proteins (Gether 2000), with numerous intermediate sub-states in between (Vauquelin and Van Liefde Subsequently, opioid receptors were shown to constitutively activate Gi proteins in a membrane preparation research has revealed a more intricate understanding of GPCR behavior, extending beyond the traditional G-protein

Biased allosteric mechanisms Allosteric sites can differentially modulate G-protein and β-arrestin coupling G-protein-biased allosteric antagonists are under investigation for several GPCRs, including CCR2, CCR7 Allosteric agonists binding to intracellular sites can also promote G-protein signaling. PCO371 is a G-protein-biased allosteric agonist for the adenosine receptor A1, with the promise to improve , such as β-arrestin and G-protein transducers, is important.

In this session, you’ll gain: ✅ Proven strategies  to balance in vitro vs. in vivo testing early — when The real friction point lies downstream : translating receptor–ligand interactions into actionable development “GPCRs are nature’s prototype allosteric proteins. Everything they do is allosteric.”

Questions about how opioids impair breathing, why xylazine complicates interventions, and how receptor-level This approach makes her models not just rigorous, but translational—bridging the gap between receptor She is especially interested in mu-opioid receptor signaling  and how xylazine, as an alpha-2 adrenergic That personal loss transforms complex receptor pharmacology into something immediate and human.

Bigger Picture: GPCR Science Meets Public Health At its core, Catherine Demery’s research  is about receptors and signaling pathways—how mu-opioid  and alpha-2 adrenergic receptors  interact to disrupt breathing Fentanyl, through the mu-opioid receptor, blunts the brainstem’s inspiratory drive so that each breath By displacing opioids from the mu-opioid receptor, it restores breathing within minutes. But that mechanism has no impact on xylazine, which works through alpha-2 adrenergic receptors.

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 There is excitement about combining pHSense with other HTRF assays for multi-pathway mapping—G protein

Crystal structures suggest ligand access to the orthosteric binding site of MT1 and MT2 receptors through entry route for 2-iodomelatonin, a nonselective agonist with a slower dissociation rate from the MT2 receptor which revealed different trajectories passing through the gap between TM helices IV and V for both receptors The side-chain flexibility of Tyr5.38 was significantly different in the two receptor subtypes, as assessed is a way of connecting the orthosteric binding site and the membrane core for lipophilic melatonin receptor

Breakthroughs this week: 12th Adhesion GPCR Workshop (Düsseldorf, Sept 16–18, 2026); Free fatty acid receptor 2 allosterism is defined by cellular context; Conformational biosensors delineate endosomal G protein These sessions span foundational pharmacology, receptor biology, modeling, translational strategy, and highlights how membrane context reshapes receptor behavior. Bitter taste receptors extend beyond taste biology.

Breakthroughs this week: New work clarifies how active-state GPCR conformations can support coupling Must-read publications:  Studies on active-state GPCR ensembles and their transducer coupling, biased angiotensin receptor ligands, and circuit-selective analgesia in pain models. The Revvity team asked a harder question: What if you could measure receptor internalization in native Subtype specificity:  selectively track receptor subtypes in complex brain tissue.

by sea bass gonadotropin-inhibitory hormone peptides in COS-7 cells transfected with their cognate receptor significantly decreased forskolin-elicited CRE-luc activity in COS-7 cells transfected with their cognate receptor Notably, GnIH2 antagonized Kiss2-evoked CRE-luc activity in COS-7 cells expressing GnIHR and Kiss2 receptor

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 (

Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR)

When pharmacologists misinterpret how an antagonist interacts with its receptor, the consequences ripple But if the antagonist binds tightly and dissociates slowly, the receptor remains blocked, even at high Antagonist “hogs” the receptor, depressing the response, even if more agonist is added. Common misconceptions  arise when irreversible binding, receptor reserve, or allosteric effects mimic He challenges the idea that curve shape alone is diagnostic, pointing out how features like receptor

The A2A adenosine receptor (A2AAR) is one of four adenosine receptor subtypes expressed in the human Saturation binding experiments on NanoLuc®-tagged A2A receptors. G.; Fazio, F. Adenosine Receptors and Their Ligands. Naunyn-Schmied. Arch. Introduction to Adenosine Receptors as Therapeutic Targets.

While some receptors selectively activate specific G protein families, others are more versatile, yielding diverse responses based on cell-specific G protein expression. Apart from G proteins, GPCRs engage other effectors for signaling modulation. Originally recognized for inhibiting G protein signaling, they also influence specific pathways such G. 2021).

Consider calcium flux assays: Teams often ask how to define fractional receptor activation, similar to A ligand may show identical EC₅₀ values in two assays while engaging receptors through very different Kenakin reveals how scaled pharmacological metrics allow teams to interpret receptor signaling changes poor solubility preventing absorption rapid clearance eliminating exposure sequestration in tissues or proteins Pharmacologists contribute: rigorous assay interpretation mechanistic insight into receptor signaling

2026 GPCR Pharmacology AMA: Receptor Theory, Biased Signaling & Assay Interpretation The first GPCR Pharmacology Kenakin will address receptor theory, assay interpretation, biased signaling, and practical drug discovery Short conceptual breakdowns Focused receptor theory discussions Clear explanations reinforcing disciplined What seems definitive during early screening can shift as assay systems, receptor expression levels, scientific discussion A continually expanding on-demand archive Sustained exposure to quantitative receptor

It began with an unmet need: how to track Gq-coupled GPCR activity without the mess of calcium flux or shown in beta cells 🚀 2025: Revvity launches pHSense A Day That Changed Everything: The Endogenous Receptor s second “aha” moment with pHSense came the day his team showed internalization of endogenous GLP-1 receptors It validated the broader goal: giving scientists tools to study receptors in their native, unmodified