Intracellular calcium ([Ca2+]i) signaling is a critical regulator of chondrogenesis, chondrocyte differentiation known to direct processes that govern chondrocyte gene expression, protein synthesis, cytoskeletal remodeling One such platform is the chemogenetic DREADD (designer receptor exclusively activated by designer drugs This study demonstrated Gαq-G-protein coupled receptor (GPCR)-mediated [Ca2+]i signaling involvement Read full article

(GPCRs) named the MT1 receptor, which couples to both Gq and Gi proteins, and the MT2 receptor, which We investigated whether melatonin receptors are expressed on airway smooth muscle; whether they regulate knockdown of the MT2 receptor by its specific siRNA. muscle tone via reduced cAMP production and increased [Ca2+]i. Read full article

September 2022 "In the Wnt-β-catenin pathway, Wnt binding to Frizzled (Fzd) and LRP5 or LRP6 (LRP5/6) co-receptors Polymerization of Dvl at the plasma membrane recruits the β-catenin destruction complex, enabling the the recruitment of Dvl to the plasma membrane. to Wnt and which is required for LRP5/6 phosphorylation. Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 A NanoBRET-Based H 3 R Conformational Biosensor to Study Real-Time H 3 Receptor Pharmacology 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 allowed the detection of both (partial) agonism and inverse agonism on living cells in a microplate reader Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected to inverse agonism "Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various Here, we revealed that dimerization of β2-AR is responsible for the constitutive activity of β2-AR generating A Gαs preferentially interacts with dimeric β2-AR, but not monomeric β2-AR, in a resting state, resulting in the production of a resting cAMP level.

(β2-adrenergic receptor and CRF2 receptor) and studied the acute metabolic effects of activating these receptors in vivo by highly selective agonists (clenbuterol and urocortin 2 (UCN2), respectively). appear primarily mediated by altered insulin release. expressed by pancreatic islets where they modulate insulin release. Read full article

April 2022 Trevena Receives up to $40M in OLINVYK ex-US Royalty-Based Financing from R-Bridge Healthcare patients with central nervous system (CNS) disorders, today announced that the Company entered into a royalty-based financing with an affiliate of R-Bridge Healthcare Fund (the R-Bridge Financing)." Read more at the source #DrGPCR #GPCR #IndustryNews

UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production Read more at the source #DrGPCR #GPCR #IndustryNews

Biased receptor signaling in drug discovery. Pharmacological Reviews, 71(2), 267-315. Sugiura, R., Satoh, R., & Takasaki, T. (2021). ERK: a double-edged sword in cancer. Spatiotemporal regulation of the p42/p44 MAPK pathway. Biology of the Cell, 93(1‐2), 71-79. M., & Lefkowitz, R. J. (2003). signal-regulated kinases 1 and 2.

the vasopressin receptor 2 (V2R). , R., Vieira-Rocha, M. M., & Lefkowitz, R. J. (2003). signal-regulated kinases 1 and 2. E., French, R. P., Lowy, A. M., & Murray, F. (2018).

explain the discovery of a novel inverse agonist at the cannabinoid receptor 2. Di Roberto, R. B., Chang, B., & Peisajovich, S. G. (2017). Kosar, M., Sarott, R. C., Sykes, D. A., Viray, A. E., Vitale, R. Flipping the GPCR switch: Structure-based development of selective cannabinoid receptor 2 inverse agonists Extracellular loop 2 of the adenosine A1 receptor has a key role in orthosteric ligand affinity and agonist

These receptors respond to a variety of signals by undergoing structural changes that activate internal Papasergi-Scott and colleagues has made significant progress in this area 2. and its separation from the receptor. Premont, R. T. & Gainetdinov, R. R. Physiological roles of G protein-coupled receptor kinases and arrestins.

September 2022 β2-Adrenergic Receptor Expression and Intracellular Signaling in B Cells Are Highly Dynamic Adrenergic receptors on B cells and intracellular β2-ADR downstream molecules (G protein-coupled receptor kinase 2 (GRK-2), β-Arrestin 2, p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP The second messengers studied (p38, ERK1/2 and CREB) followed a biphasic course, characterized by a reduction Read more at the source #DrGPCR #GPCR #IndustryNews

Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. of the damage following ischemia-reperfusion, the regulation of blood pressure, and the restriction of cardiac remodeling. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great

receptors (GPCRs) can be regulated by PKC. Additionally, using the Gαq/11 inhibitor YM-254890, GPCR kinase 2 and 3 (GRK2 and GRK3) KO cells, and a receptor containing a mutated putative adaptor protein complex 2 (AP-2) interaction motif, we demonstrate that internalization of rat mGlu5a is mediated by Gαq/11 proteins (77% of the response), GRK2 (27%), and AP-2 (29%), but not GRK3.

Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. of the damage following ischemia-reperfusion, the regulation of blood pressure, and the restriction of cardiac remodeling. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great

We close registrations in 2 weeks!! from September 30th to October 6th, 2024 Industry News Nxera Pharma appoints experienced commercial R& in the Trafficking of Group I Metabotropic Glutamate Receptors Dual regulation of IP3 receptors by IP3 Molecular Insights into GPCR Function LYCHOS is a human hybrid of a plant-like PIN transporter and a GPC R Biochemical characterization of Prokineticin 2 binding to Prokineticin receptor 1 in zebrafish Coupling

August 2022 "Emerging evidence suggests that G protein-coupled receptor (GPCR) kinases (GRKs) are associated Significantly, we show that GRKs generate distinct phosphorylation barcodes in intracellular loop 2 ( ICL2) and the C terminus of APH1A, which differentially regulate recruitment of the scaffolding protein β-arrestin 2 (βarr2) to APH1A and γ-secretase-mediated Aβ generation. Read more at the source #DrGPCR #GPCR #IndustryNews

Over the past 2 decades, pepducins have progressed initially from pharmacologic tools used to manipulate site-independent manner to compounds with therapeutic potential that have even been used safely in phase 1 and 2 This review will focus in particular on pepducins designed from protease-activated receptors, C-X-C motif chemokine receptors, formyl peptide receptors, and the β2-adrenergic receptor. Read more at the source #DrGPCR #GPCR #IndustryNews

receptors (GPCRs), such as adrenergic receptors and AngII receptors. In this review, we discuss important aspects of adrenal GPCR signaling and regulation, as they pertain to modulation of cardiac function in the context of chronic HF, by focusing on the 2 best studied adrenal GPCR types in that context, adrenergic receptors and AngII receptors (AT 1 Rs). of the GPCR-kinases and the β-arrestins in the adrenals, 2 protein families that regulate the signaling

trigger receptor internalization via interaction with the adaptor protein 2 (AP2) and clathrin heavy M., Medel-Lacruz, B., Baidya, M., Makarova, M., Mistry, R., Goulding, J., Drube, J., Hoffmann, C., Owen ., Kise, R., Barsi-Rhyne, B., Siepe, D. H., Heydenreich, F. Neurosci. 2, 727–733. https://doi.org/10.1038/35094577. Pharmacology & therapeutics, 89(2), 139–147. https://doi.org/10.1016/s0163-7258(00)00107-8

phosphorylation have been pivotal in deciphering GPCR activity, particularly in drug discovery endeavors [2] The emergence of resonance energy transfer (RET) techniques, notably Fluorescence Resonance Energy Transfer Annu Rev Biochem, 1987. 56: p. 615-49. 2.      Nat Methods, 2005. 2(3): p. 177-84. 7.      Janicot, R., et al., Direct interrogation of context-dependent GPCR activity with a universal biosensor

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined as a regulator of appetite/hunger balance mechanisms mostly up to date. In this review paper, we aimed to point out the importance of the MC3R regulations in three main concepts : 1) its impact on weight and appetite control, 2) the control of growth, puberty, and circadian rhythm Read more at the source #DrGPCR #GPCR #IndustryNews

recruiting GPR84 agonists "In order to avoid a prolonged pro-inflammatory neutrophil response, signaling downstream of an agonist-activated G protein-coupled receptor (GPCR) has to be rapidly terminated. 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 in neutrophils, play a key role in regulating inflammation.

and insulin secretion, making it a well-established target for treating type 2 diabetes and obesity [2]. Denise Wootten and colleagues has highlighted the importance of extracellular loop 2 (ECL2) in stabilizing Nat Rev Drug Discov, 2013. 12 (3): p. 205-16. 2.          Anson, M., et al., Incidence of new onset type 2 diabetes in adults living with obesity treated with

T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. C., Ring, A. R., Venkatakrishnan, A. J., Jude, K. M., Dukkipati, A., Feinberg, E. ., Dror, R. O., Ploegh, H. L., & Garcia, K. C. (2015). Structural biology.

Thus, we investigated the regulatory functions of its β-adrenergic-like octopamine receptor (PxOctβ3) the receptor mRNA were determined. Furthermore, the agonists naphazoline, clonidine, 2-phenethylamine, and amitraz activated the PxOctβ3 receptor, and naphazoline was the most effective. The injection of double-stranded RNA in an RNA interference assay indicated that PxOctβ3 regulates development

diabetes insipidus "Loss-of-function mutations of the arginine vasopressin receptor 2 gene (AVPR2) cause Recent studies showed that some AVPR2 mutations could cause biased Gαq/11 protein coupling rather than Investigation into the characterization of biased receptors may give insights into the relationship between the conformational change of the receptor because of the mutation and related downstream signaling. R68W showed bias to coupling with Gαq/11 protein rather than V162A and wild-type receptor.