keyword
MENU ▼
Read by QxMD icon Read
search

G protein coupled receptor

keyword
https://www.readbyqxmd.com/read/28820879/a-kinetic-view-of-gpcr-allostery-and-biased-agonism
#1
J Robert Lane, Lauren T May, Robert G Parton, Patrick M Sexton, Arthur Christopoulos
G-protein-coupled receptors (GPCRs) are one of the most tractable classes of drug targets. These dynamic proteins can adopt multiple active states that are linked to distinct functional outcomes. Such states can be differentially stabilized by ligands interacting with the endogenous agonist-binding orthosteric site and/or by ligands acting via spatially distinct allosteric sites, leading to the phenomena of 'biased agonism' or 'biased modulation'. These paradigms are having a major impact on modern drug discovery, but it is becoming increasingly apparent that 'kinetic context', at the level of both ligand-receptor and receptor-signal pathway kinetics, can have a profound impact on the observation and quantification of these phenomena...
August 18, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28820061/renin-angiotensin-system-and-cytokines-in-chronic-kidney-disease-clinical-and-experimental-evidence
#2
Ariadna Andrade Saldanha Silva, Beranardo Bahia Finotti, Amanda Oliveira Lauar, Thiago Ruiz Rodrigues Prestes, Ana Cristina Simões E Silva
Chronic kidney disease (CKD) has become a major public health problem in Brazil and worldwide. There are many causes of CKD, being the congenital anomalies of the kidney and urinary tract and the glomerular diseases very common in pediatric patients, while diabetic nephropathy, CKD due to chronic arterial hypertension and glomerular diseases are predominant in adult patients. Many endogenous mediators have been related to the pathophysiology of CKD, being relevant the effects of the renin-angiotensin system (RAS) and the immune-inflammatory mediators including cytokines...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28819396/expression-and-significances-of-g-protein-coupled-receptor-kinase-3-in-hepatocellular-carcinoma
#3
Ye Jin, Zhi-Yong Liang, Wei-Xun Zhou, Li Zhou
Objective: To investigate expression, clinical, pathologic and prognostic significances of G-protein-coupled receptor kinase 3 (GRK3) in hepatocellular carcinoma (HCC). Materials and Methods: Expression of GRK3 was detected using Western blotting and tissue microarray-based immunohistochemical staining in 8 and 395 patients (training set: n=164; validation set: n=231) with HCC underwent hepatectomy, respectively. GRK3 expression and its associations with cliniopathologic variables and tumor-specific survival were evaluated...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818718/template-selection-and-refinement-considerations-for-modelling-aminergic-gpcr-ligand-complexes
#4
Kaniz F Urmi, Angela M Finch, Renate Griffith
G protein-coupled receptors (GPCRs) are important targets for development of drugs for the treatment of many diseases. However, crystal structures are available for only a small fraction of these membrane bound proteins. Accurate homology models will provide opportunities for effective drug design targeting GPCRs. Recently, several serotonin receptor crystal structures were solved and needed to be evaluated as potential templates. In the first part of this work different measures of similarity in template selection were explored and methods for homology modelling, docking and refinement of aminergic GPCR-ligand complexes were developed and evaluated by comparing models of the D3-R/eticlopride complex with the crystal structure...
July 31, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28818206/pharmacological-and-activated-fibroblast%C3%A2-targeting-of-g%C3%AE-%C3%AE-grk2-after%C3%A2-myocardial-ischemia-attenuates-heart-failure-progression
#5
Joshua G Travers, Fadia A Kamal, Iñigo Valiente-Alandi, Michelle L Nieman, Michelle A Sargent, John N Lorenz, Jeffery D Molkentin, Burns C Blaxall
BACKGROUND: Cardiac fibroblasts are a critical cell population responsible for myocardial extracellular matrix homeostasis. Upon injury or pathological stimulation, these cells transform to an activated myofibroblast state and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation, a hallmark of heart failure (HF), induces pathological signaling through G protein βγ (Gβγ) subunits and their interaction with G protein-coupled receptor kinase 2 (GRK2)...
August 22, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28817612/expression-and-functional-implications-of-the-renal-apelinergic-system-in-rodents
#6
Anne-Marie O'Carroll, Sabrine Salih, Philip R Griffiths, Aarifah Bijabhai, Mark A Knepper, Stephen J Lolait
Apelin binds to the G protein-coupled apelin receptor (APJ; gene name aplnr) to modulate diverse physiological systems including cardiovascular function, and hydromineral and metabolic balance. Recently a second endogenous ligand for APJ, named apela, has been discovered. We confirm that apela activates signal transduction pathways (ERK activation) in cells expressing the cloned rat APJ. Previous studies suggest that exogenous apela is diuretic, attributable wholly or in part to an action on renal APJ. Thus far the cellular distribution of apela in the kidney has not been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28815513/an-update-on-p2y13-receptor-signalling-and-function
#7
Raquel Pérez-Sen, Rosa Gómez-Villafuertes, Felipe Ortega, Javier Gualix, Esmerilda G Delicado, María Teresa Miras-Portugal
The distribution of nucleotide P2Y receptors across different tissues suggests that they fulfil key roles in a number of physiological and pathological conditions. P2Y13 is one of the latest P2Y receptors identified, a novel member of the Gi-coupled P2Y receptor subfamily that responds to ADP, together with P2Y12 and P2Y14. Pharmacological studies drew attention to this new ADP receptor, with a pharmacology that overlaps that of P2Y12 receptors but with unique features and roles. The P2RY12-14 genes all reside on human chromosome 3 at 3q25...
August 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815512/p2y2-receptor-functions-in-cancer-a-perspective-in-the-context-of-colorectal-cancer
#8
Fernand-Pierre Gendron, Morgane Placet, Guillaume Arguin
Purinergic signaling has recently emerged as a network of signaling molecules, enzymes and receptors that coordinates the action and behavior of cancerous cells. Extracellular adenosine 5' triphosphate activates a plethora of P2 nucleotide receptors that can putatively modulate cancer cell proliferation, survival and dissemination. In this context, the G protein-coupled P2Y2 receptor was identified as one of the entities coordinating the cellular and molecular events that characterize cancerous cells. In this chapter, we will look at the contribution of the P2Y2 receptor in cancer outcomes and use this information to demonstrate that the P2Y2 receptor represents a drug target of interest in the setting of colorectal cancer, for which the role and function of this receptor is poorly defined...
August 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814745/suppression-of-grk2-expression-reduces-endothelial-dysfunction-by-restoring-glucose-homeostasis
#9
Kumiko Taguchi, Mari Hida, Mami Hasegawa, Haruka Narimatsu, Takayuki Matsumoto, Tsuneo Kobayashi
Despite the associations between diabetic complications and vascular endothelial dysfunction, a direct therapeutic method targeting endothelial dysfunction remains poorly characterized. We have previously shown that chemical inhibition of G-protein-coupled receptor kinase 2 (GRK2) slightly enhances insulin sensitivity and reduces endothelial dysfunction in type 2 diabetic mice. In this study, we identified GRK2 as a novel therapeutic target of diabetic endothelial dysfunction and investigated the effect on diabetic endothelial dysfunction through the systemic administration of GRK2 siRNA using a hydrodynamic-based procedure, resulting in suppression of increased GRK2 protein levels in the liver...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813513/validation-of-commercial-mas-receptor-antibodies-for-utilization-in-western-blotting-immunofluorescence-and-immunohistochemistry-studies
#10
Valeria Burghi, Natalia Cristina Fernández, Yamila Belén Gándola, Verónica Gabriela Piazza, Diego Tomás Quiroga, Érica Guilhen Mario, Janaína Felix Braga, Michael Bader, Robson Augusto Souza Santos, Fernando Pablo Dominici, Marina Cecilia Muñoz
Mas receptor (MasR) is a G protein-coupled receptor proposed as a candidate for mediating the angiotensin (Ang)-converting enzyme 2-Ang (1-7) protective axis of renin-angiotensin system. Because the role of this receptor is not definitively clarified, determination of MasR tissue distribution and expression levels constitutes a critical knowledge to fully understanding its function. Commercially available antibodies have been widely employed for MasR protein localization and quantification, but they have not been adequately validated...
2017: PloS One
https://www.readbyqxmd.com/read/28813418/mechanism-of-intracellular-allosteric-%C3%AE-2ar-antagonist-revealed-by-x-ray-crystal-structure
#11
Xiangyu Liu, Seungkirl Ahn, Alem W Kahsai, Kai-Cheng Meng, Naomi R Latorraca, Biswaranjan Pani, A J Venkatakrishnan, Ali Masoudi, William I Weis, Ron O Dror, Xin Chen, Robert J Lefkowitz, Brian K Kobilka
G-protein-coupled receptors (GPCRs) pose challenges for drug discovery efforts because of the high degree of structural homology in the orthosteric pocket, particularly for GPCRs within a single subfamily, such as the nine adrenergic receptors. Allosteric ligands may bind to less-conserved regions of these receptors and therefore are more likely to be selective. Unlike orthosteric ligands, which tonically activate or inhibit signalling, allosteric ligands modulate physiologic responses to hormones and neurotransmitters, and may therefore have fewer adverse effects...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28811548/ligand-binding-modes-from-low-resolution-gpcr-models-and-mutagenesis-chicken-bitter-taste-receptor-as-a-test-case
#12
Antonella Di Pizio, Louisa-Marie Kruetzfeldt, Shira Cheled-Shoval, Wolfgang Meyerhof, Maik Behrens, Masha Y Niv
Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811382/an-engineered-s1p-chaperone-attenuates-hypertension-and-ischemic-injury
#13
Steven L Swendeman, Yuquan Xiong, Anna Cantalupo, Hui Yuan, Nathalie Burg, Yu Hisano, Andreane Cartier, Catherine H Liu, Eric Engelbrecht, Victoria Blaho, Yi Zhang, Keisuke Yanagida, Sylvain Galvani, Hideru Obinata, Jane E Salmon, Teresa Sanchez, Annarita Di Lorenzo, Timothy Hla
Endothelial dysfunction, a hallmark of vascular disease, is restored by plasma high-density lipoprotein (HDL). However, a generalized increase in HDL abundance is not beneficial, suggesting that specific HDL species mediate protective effects. Apolipoprotein M-containing HDL (ApoM(+)HDL), which carries the bioactive lipid sphingosine 1-phosphate (S1P), promotes endothelial function by activating G protein-coupled S1P receptors. Moreover, HDL-bound S1P is limiting in several inflammatory, metabolic, and vascular diseases...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28811233/stimulation-of-ovarian-cell-proliferation-by-tetrabromobisphenol-a-but-not-tetrachlorobisphenol-a-through-g-protein-coupled-receptor-30
#14
Marta Hoffmann, Justyna Gogola, Małgorzata Kotula-Balak, Anna Ptak
Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are bisphenol A (BPA) analogs, where the phenolic moieties are substituted with halogens (Br or Cl). Previous studies indicate that BPA has significant proliferative effects on in vitro cultured epithelial ovarian cancer (EOC) cells. Considering this, we analyzed the effects of both TBBPA and TCBPA at 1, 10, and 50nM on ovarian cancer cell proliferation. The majority of malignant ovarian tumors are epithelial in origin, but approximately 10% are classified as ovarian sex cord tumors, with the most common type being granulosa cell tumors (GCTs)...
August 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28810246/gper-agonist-g1-attenuates-neuroinflammation-and-dopaminergic-neurodegeneration-in-parkinson-disease
#15
Jing Guan, Beibei Yang, Yi Fan, Ji Zhang
OBJECTIVE: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD...
August 16, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28808992/a-photoaffinity-labeling-based-chemoproteomics-strategy-for-unbiased-target-deconvolution-of-small-molecule-drug-candidates
#16
Jason R Thomas, Scott M Brittain, Jennifer Lipps, Luis Llamas, Rishi K Jain, Markus Schirle
The combination of photoaffinity labeling (PAL) and quantitative chemoproteomics enables the comprehensive, unbiased determination of protein interaction profiles to support target identification of bioactive small molecules. This approach is amenable to cells in culture and compatible with pharmacologically relevant transmembrane target classes like G-protein coupled receptors and ions channels which have been notoriously hard to access by conventional chemoproteomics approaches. Here, we describe a strategy that combines PAL probe titration and competition with excess parental compounds with the goal of enabling the identification of specific interactors as well as assessing the functional relevance of a binding event for the phenotype under investigation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808053/navigating-the-conformational-landscape-of-g-protein-coupled-receptor-kinases-during-allosteric-activation
#17
Xin-Qiu Yao, M Claire Cato, Emily Labudde, Tyler S Beyett, John J G Tesmer, Barry J Grant
G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808008/mathematical-model-reveals-role-of-nucleotide-signaling-in-airway-surface-liquid-homeostasis-and-its-dysregulation-in-cystic-fibrosis
#18
Conner I Sandefur, Richard C Boucher, Timothy C Elston
Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28806758/developmental-vascular-remodeling-defects-and-postnatal-kidney-failure-in-mice-lacking-gpr116-adgrf5-and-eltd1-adgrl4
#19
Shun Lu, Shuya Liu, Astrid Wietelmann, Baktybek Kojonazarov, Ann Atzberger, Cong Tang, Ralph Theo Schermuly, Hermann-Josef Gröne, Stefan Offermanns
GPR116 (ADGRF5) and ELTD1 (ADGRL4) belong to different subfamilies of the adhesion G-protein-coupled receptor group but are both expressed in endothelial cells. We therefore analyzed their functions in mice lacking these receptors. While loss of GPR116 or ELTD1 alone had no obvious effect on cardiovascular or kidney function, mice lacking both, GPR116 and ELTD1, showed malformations of the aortic arch arteries and the cardiac outflow tract leading to perinatal lethality in about 50% of the mutants. In addition to cardiovascular malformations, surviving mice developed renal thrombotic microangiopathy as well as hemolysis and splenomegaly, and their lifespan was significantly reduced...
2017: PloS One
https://www.readbyqxmd.com/read/28806271/luminal-chemosensing-in-the-gastroduodenal-mucosa
#20
Izumi Kaji, Jonathan D Kaunitz
PURPOSE OF REVIEW: We report recently published knowledge regarding gut chemosensory mechanisms focusing on nutrient-sensing G protein-coupled receptors (GPCRs) expressed on gut enteroendocrine cells (EECs), tuft cells, and in afferent nerves in the gastroduodenal mucosa and submucosa. RECENT FINDINGS: Gene profiling of EECs and tuft cells have revealed expression of a variety of nutrient-sensing GPCRs. The density of EEC and tuft cells is altered by luminal environmental changes that may occur following bypass surgery or in the presence of mucosal inflammation...
August 12, 2017: Current Opinion in Gastroenterology
keyword
keyword
98066
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"