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Imagine running a calcium assay and discovering your compound shows only weak activity. Terry Kenakin dives deep into a widely used, often misunderstood tool in early drug discovery: the calcium You’ll learn why calcium signals are inherently transient—giving rise to a “hemi-equilibrium” window Because when true pharmacological profiling is essential—like detecting partial or inverse agonism—calcium Unlock "Calcium Assays" now

Intracellular calcium ([Ca2+]i) signaling is a critical regulator of chondrogenesis, chondrocyte differentiation Calcium (Ca2+) signaling is known to direct processes that govern chondrocyte gene expression, protein Control of chondrocyte/chondroprogenitor Ca2+ signaling has been attempted through mechanical and/or Synthetic signaling platforms permitting precise and selective Ca2+ signal transduction can improve dissection of the roles that [Ca2+]i signaling plays in chondrocyte behavior.

Ca2+ (Ca2+o ) via a dimeric extracellular Venus flytrap (VFT) unit that activates G protein-dependent signaling corresponding to heterozygous familial hypocalciuric hypercalcemia type-1 (FHH-1), supported maximal signaling In contrast, a single WT HH bundle was insufficient for maximal signaling and there was no functional Finally, we observed that the Ca2+o -stimulated CaSR operated exclusively via signaling in-trans and not via combined in-trans and in-cis signaling.

vast family of membrane-bound proteins crucial for transmitting external stimuli into intracellular signals cells lacking Gs proteins, a study by Stallaert et al. in 2017 showed that Gs played a pivotal role in calcium signalling at the β2-adrenergic receptors (β2AR) [4]. Overall, the increased calcium signalling was attributed to the release of ATP via β2AR-Gs mediated activation Gupte, T.M., et al., Priming GPCR signaling through the synergistic effect of two G proteins. 

However, basic physiology of PFC astrocytes, including which neuromodulatory signals they respond to Here, we characterize divergent signaling signatures in mouse astrocytes of the PFC and primary sensory Instead, fast calcium signals in PFC astrocytes are time locked to dopamine release and are mediated Thus, we identify astrocytes as active players in dopaminergic signaling in the PFC, contributing to

When it comes to signal transduction, cellular context matters. can be activated by ligands and initiate signaling cascades. Activation of nuclear GPCRs, such as the metabotropic glutamate receptor 5 (mGluR5), can lead to sustained calcium , sustained signaling responses from intracellular compartments can be regulated by the kinetics of signaling Compartmentalized GPCR Signaling from Intracellular Membranes.

Joseph Crecelius , Sara Benzow , Adriano Marchese Cannabinoid regulation of angiotensin II-induced calcium , Gemma Navarro , José Labandeira-García , Rafael Franco Endomembrane GPCR signaling: 15 years on, signalling GPCR: Structural Insights and Role in Drug Discovery Orion Biotechnology has a new website signaling in striatal neurons Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics GPCRs in Oncology and Immunology Gallein, G protein βγ subunits inhibitor, suppresses

bridge foundational receptor theory with today’s most pressing pharmacological questions, from biased signaling Read Maria’s Story GPCR Publication Highlights   CXCR4 signaling promotes terminal erythropoiesis  through nuclear translocation and perinuclear calcium bursts. 

Biased signalling and allosteric machines: new vistas and challenges for drug discovery. Allosteric modulation of G protein-coupled receptor signaling. Biased Receptor Signaling in Drug Discovery. Pharmacol Rev. 2019;71(2):267-315. 33.         Science signaling. 2024;17(841):eadi4747. 37.         Science signaling. 2024;17(843):eabq7038. 38.        

It’s about chasing a signal through the noise. She went from reluctant intern to global researcher shaping how we understand GPCR spatial signaling. Luck, Leadership & GPCR Signaling Michelle is clear: luck played a role. But so did choice. of Signaling laboratory, asking a deceptively simple question: where  do GPCR signals happen—and how Spatial signaling isn’t just a technical detail. It’s a new language for drug discovery.

paper highlights: GLP-1R/GIPR biased agonism enhances metabolic outcomes Ghrelin receptor flips D2 signaling emphasizes scaffold selection, linker optimization, and assay compatibility to enhance target binding and signal Constitutive ghrelin receptor activity, not dimerization or ligand binding —reverses dopamine D2 signaling A MOR-positive allosteric modulator (BMS-986122) selectively enhances opioid signaling  through specific

Regulator G protein Signaling (RGS) proteins are critical components of the intracellular signaling pathways and amplitude of GPCR signaling. Another signaling pathway related to RGS4 involves the regulation of the immune response. Senese, N.B., et al., Regulator of G-Protein Signaling (RGS) Protein Modulation of Opioid Receptor Signaling Hepler, Cellular regulation of RGS proteins: modulators and integrators of G protein signaling.

elevation and voltage-dependent current generated by MRGPRB2 activation were correlated with extracellular calcium The voltage-dependent current induced by MRGPRB2 was inhibited by calcium-activated chlorine channel Our results indicated the involvement of the PLC-IP3-ORAI signaling pathway and CACCS in MRGPRB2-mediated

bound to these interaction partners available today do not reveal a clear conformational basis for signaling

One fascinating aspect of the cellular signaling network is the crosstalk between G protein-coupled receptors while promoting constitutive Gβγ signaling. localization and signaling efficiency. intervention in diseases characterized by dysregulated signaling pathways. Science signaling, 17(839), eade8041. https://doi.org/10.1126/scisignal.ade8041

applications of Nbs to facilitate the development of more selective drugs capable of modulating specific signaling

G protein-coupled receptors (GPCRs) activation assumes that stimulation of heterotrimeric G protein signaling In this model, GPCR signaling is turned-off by receptor phosphorylation via GPCR kinases (GRKs) and subsequent the last decade, this model has been extended by discovering that some internalized GPCRs continue to signal Accumulative evidence shows that the location of signaling has an impact on the physiological effects of GPCR signaling.

receptors are expressed on airway smooth muscle; whether they regulate intracellular cyclic AMP (cAMP) and calcium

Historically, drug discovery efforts targeting GPCRs focused on G-protein-dependent signaling pathways , such as those involving cAMP and calcium mobilisation, to identify lead compounds. family, have long been known to play a critical role in the signaling pathways of GPCRs. This signaling cascade involves several steps. Biased receptor signaling in drug discovery. Pharmacological Reviews, 71(2), 267-315.

We will discuss recent evidence as well as what we consider as emerging areas to explore; from the signalling relevance of these interactions, since this additional level of molecular cross-talk between receptors and signaling

regulation of mTORC1 by upstream stimuli, with a specific focus on G-protein coupled receptor (GPCR) signaling

events, including the modulation of cyclic adenosine monophosphate (cAMP), calcium mobilization, and extracellular signal-regulated kinase (ERK) activation [1]. Traditionally, second messenger assays measuring cAMP accumulation, calcium mobilization, and ERK phosphorylation due to pathway crosstalk and signal amplification [3]. Gilman, A.G., G proteins: transducers of receptor-generated signals. 

Opioid receptors belong to class A of G protein-coupled receptors or GPCRs and signaled mainly through Therefore, the study of the different signal transductions triggered by the opioid-receptor interaction downstream through different signaling pathways triggered by different molecules2. Therefore to understand better the functions of arrestins in MOR signaling, Shiraki et al., explored the function of β-arrestin 2 in MOR signaling using the SH-SY5Y cell line that endogenously expresses

protein-coupled receptors (GPCRs) are membrane-bound proteins that sense external stimuli and relay signals For example, dimerization has been shown to affect signaling pathways in class A dopamine receptors like homodimers and heterodimers, which may play a crucial role in modulating receptor function and ligand signaling decreased high-affinity binding to its natural ligand, GLP-1, while selectively affecting receptor signaling Perreault, M.L., et al., Heteromeric dopamine receptor signaling complexes: emerging neurobiology and

October 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing prevalence presents treatment challenges. Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis or effectively address the associated cognitive and memory deficits. Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer's disease. The adenosine A1 and A2A receptors are expressed in the human brain and have a proposed involvement in the pathogenesis of dementia. Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst improving cognition and memory. In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic potential of A1 and A2A receptors. Although there are no available medicines targeting these receptors approved for treating dementia, we provide insights into some novel strategies, including allosterism and the targeting of oligomers, which may increase drug discovery success and enhance the therapeutic response." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing prevalence presents treatment challenges. Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis or effectively address the associated cognitive and memory deficits. Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer's disease. The adenosine A1 and A2A receptors are expressed in the human brain and have a proposed involvement in the pathogenesis of dementia. Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst improving cognition and memory. In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic potential of A1 and A2A receptors. Although there are no available medicines targeting these receptors approved for treating dementia, we provide insights into some novel strategies, including allosterism and the targeting of oligomers, which may increase drug discovery success and enhance the therapeutic response." Read more at the source #DrGPCR #GPCR #IndustryNews

Prostaglandin (PG) signaling regulates a wide variety of physiological and pathological processes, including Many G-protein-coupled receptors (GPCRs) including EP4 are localized in cilia for modulating cAMP signaling During development, PGE2 signaling regulates embryogenesis, hepatocyte differentiation, hematopoiesis This review outlines recent advances in understanding the functions and mechanisms of prostaglandin signaling

Rho1 signaling is activated by G-protein-coupled receptor (GPCR) signaling at the cell surface. embryonic salivary gland (SG) invagination, the GPCR ligand Folded gastrulation (Fog) activates Rho1 signaling The SG receptor that transduces the Fog signal into Rho1-dependent myosin activation has not been identified Here, we reveal that the Smog GPCR transduces Fog signal to regulate Rho kinase accumulation and myosin

Although they form an ancient signaling system, there is still a great deal of variety in neuropeptides Additionally, we discovered that the neuropeptide signaling systems of Sternorrhyncha were very different groundwork for the creation of novel D. vitifoliae management strategies that specifically target these signaling

The Era of Cold Fingers and Patience Back then, GPCR signaling experiments weren’t elegant; they were Reading those first papers on GPCR signaling organization absolutely fascinated me — the idea that receptors What Changed After This : High-throughput capabilities meant researchers could map GPCR signaling more The field moved from single readouts to integrated signaling landscapes, accelerating drug discovery now it’s the foundation — a starting point for more ambitious questions about GPCR networks, biased signaling