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https://www.readbyqxmd.com/read/30516351/adenosine-2a-receptor-signals-block-autoimmune-arthritis-by-inhibiting-pathogenic-germinal-center-t-follicular-helper-cells
#1
Shirdi E Schmiel, Lokesh A Kalekar, Na Zhang, Thomas W Blankespoor, Londyn J Robinson, Daniel L Mueller
OBJECTIVE: CD4 germinal center (GC)-T follicular helper (Tfh) cells are important in the pathogenesis of autoimmune arthritis. Previous studies have shown that adenosine 2a receptor (A2aR, Adora2a) signaling can divert CD4 T cells away from the GC-Tfh cell lineage during the primary response to foreign antigens. Therefore, we examined the effects of A2aR signaling on CD4 T cells during the recognition of a self-antigen using a mouse model of autoimmune arthritis. METHODS: Wild type and Adora2a-deficient KRN TCR-transgenic CD4 T cells specific for glucose-6-phosphate isomerase (GPI)/I-Ag7 were transferred into immunodeficient Tcra-/- I-Ag7 -expressing mice to induce arthritis...
December 5, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/30514403/purinergic-targeting-enhances-immunotherapy-of-cd73-solid-tumors-with-piggybac-engineered-chimeric-antigen-receptor-natural-killer-cells
#2
Jiao Wang, Kyle B Lupo, Andrea M Chambers, Sandro Matosevic
BACKGROUND: The anti-tumor immunity of natural killer (NK) cells can be paralyzed by the CD73-induced generation of immunosuppressive adenosine from precursor ATP within the hypoxic microenvironment of solid tumors. In an effort to redirect purinergic immunosuppression of NK cell anti-tumor function, we showed, for the first time, that immunometabolic combination treatment with NKG2D-engineered CAR-NK cells alongside blockade of CD73 ectonucleotidase activity can result in significant anti-tumor responses in vivo...
December 4, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30513816/targeting-adenosine-receptor-signaling-in-cancer-immunotherapy
#3
REVIEW
Kevin Sek, Christina Mølck, Gregory D Stewart, Lev Kats, Phillip K Darcy, Paul A Beavis
The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of 'checkpoint blockade' and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient's own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function...
December 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30513523/microrna-15-activates-nf-%C3%AE%C2%BAb-pathway-via-down-regulating-expression-of-adenosine-a2-receptor-in-ulcerative-colitis
#4
Huixia Zhang, Wei Li
BACKGROUND/AIMS: The role of miR-15 in ulcerative colitis (UC) is unclear. In this study, we found that miR-15 downregulated the expression of adenosine A2a receptor (A2aAR) in the colonic tissues of patients with UC and in HT-29 human colonic epithelial cells. METHODS: The study population comprised patients with UC (n=23), irritable bowel syndrome (IBS, n=22), and healthy subjects (n = 20). The levels of miR-15, A2aAR, and protein in colon tissue biopsies were determined by real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence staining, and Western blotting...
December 4, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30511252/impact-of-genetic-variations-in-adora2a-gene-on-depression-and-symptoms-a-cross-sectional-population-based-study
#5
Sílvia Oliveira, Ana Paula Ardais, Clarissa Ribeiro Bastos, Marta Gazal, Karen Jansen, Luciano de Mattos Souza, Ricardo Azevedo da Silva, Manuella Pinto Kaster, Diogo Rizzato Lara, Gabriele Ghisleni
Genetic variants involved in adenosine metabolism and its receptors were associated with increased risk for psychiatric disorders, including anxiety, depression, and schizophrenia. Here, we examined an association between a single nucleotide polymorphism in A2A receptor gene (ADORA2A, rs2298383 SNP) with current depressive episode and symptom profile. A total of 1253 individuals from a cross-sectional population-based study were analyzed by the Mini International Neuropsychiatric Interview 5.0. Our data showed that the TT genotype of ADORA2A rs2298383 SNP was associated with reduced risk for depression when compared to the CC/CT genotypes (p = 0...
December 3, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/30507864/physical-exercise-prevents-memory-impairment-in-an-animal-model-of-hypertension-through-modulation-of-cd39-and-cd73-activities-and-a2a-receptor-expression
#6
Andréia Machado Cardoso, Leandro Henrique Manfredi, Daniela Zanini, Margarete Dulce Bagatini, Jessié Martins Gutierres, Fabiano Carvalho, Alain Tremblay, Adriane Belló-Klein, Maribel Antonello Rubin, Vera Maria Morsch, Jean Sévigny, Maria Rosa Chitolina Schetinger
: Background: Central nervous system function has been emerging as an approach to understand hypertension-mediated memory dysfunction, and chronic exercise is able to modulate the purinergic system. METHOD: Herein, we investigated the effect of chronic swimming training on the purinergic system in cortex and hippocampus of L-NAME-induced hypertensive rats. Male Wistar rats were divided into four groups: Control, Exercise, L-NAME and Exercise L-NAME. Inhibitory avoidance test was used to assess memory status...
January 2019: Journal of Hypertension
https://www.readbyqxmd.com/read/30507034/optimization-and-pharmacological-characterization-of-receptor-mediated-g-i-o-activation-in-postmortem-human-prefrontal-cortex
#7
Yuji Odagaki, Masakazu Kinoshita, Toshio Ota, J Javier Meana, Luis F Callado, Jesús A García-Sevilla
The biochemical abnormalities in transmembrane signal transduction mediated through G protein-coupled receptors (GPCRs) have been postulated as underlying pathophysiology of psychiatric diseases such as schizophrenia and mood disorders. In the present study, the experimental conditions of agonist-induced [35 S]GTPγS binding in postmortem human brain membranes were optimized, and the responses induced by a series of agonists were pharmacologically characterized. The [35 S]GTPγS binding assay was performed in postmortem human prefrontal cortical membranes by means of filtration techniques, and standardized as to GDP concentration, membrane protein content, MgCl2 and NaCl concentrations in assay buffer, incubation period, and effect of white matter contamination...
December 3, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/30498135/mixed-reviews-for-a2ar-inhibitor-in-nsclc
#8
(no author information available yet)
Findings of a phase I/II trial of the adenosine 2A receptor blocker NIR178 combined with the PD-1 inhibitor spartalizumab in advanced non-small cell lung cancer suggest that the drugs are safe. Two of 25 patients showed complete or partial responses, and 13 had stable disease.
November 29, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30497387/compared-efficacy-of-clopidogrel-and-ticagrelor-in-treating-acute-coronary-syndrome-a-meta-analysis
#9
Dong Wang, Xiao-Hong Yang, Ji-Dong Zhang, Rui-Bin Li, Min Jia, Xiao-Ran Cui
BACKGROUND & AIMS: Ticagrelor has been acknowledged as a new oral antagonist of P2Y12-adenosine diphosphate receptor, as a strategy with more rapid onset as well as more significant platelet inhibition function in acute coronary syndrome (ACS) patients. The clinical benefit of ticagrelor compared with clopidogrel remains controversial. The current meta-analysis was conducted to better evaluate the role of ticagrelor in comparison of clopidogrel in treating ACS patients. METHODS: The publications involving the safety as well as the efficacy of clopidogrel versus ticagrelor were screened and identified updated to June 2018...
November 29, 2018: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/30482191/does-glucagon-have-a-positive-inotropic-effect-in-the-human-heart
#10
EDITORIAL
Jesus Hernández-Cascales
Glucagon is considered to exert cardiostimulant effects, most notably the enhancement of heart rate and contractility, due to the stimulation of glucagon receptors associated with Gs protein stimulation which causes adenylyl cyclase activation and the consequent increase in 3',5'-cyclic adenosine monophosphate production in the myocardium. These effects have been extensively demonstrated in experimental studies in different animal species. However, efforts to extrapolate the experimental data to patients with low cardiac output states, such as acute heart failure or cardiogenic shock, have been disappointing...
November 27, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/30481769/platelet-neutrophil-interactions-are-lower-in-cord-blood-of-premature-newborns
#11
Ijeoma Esiaba, Danilyn M Angeles, Terry-Ann M Milford, Lorena M Salto, Kimberly J Payne, Melissa Y Kidder, Danilo S Boskovic
OBJECTIVE: To quantify platelet-neutrophil interaction by flow cytometry, in newborn cord blood, as a function of gestational age. RATIONALE: Little is known about platelet function markers in the newborn, and developmental variations in these markers are not well described. METHODS: Cord blood samples were obtained from 64 newborns between 23 and 40 weeks' gestation. The neonates were grouped into three categories: preterm (< 34 weeks' gestation, n = 21), late preterm (34 to < 37 weeks' gestation, n = 22), and term (≥37 weeks' gestation, n = 21)...
November 27, 2018: Neonatology
https://www.readbyqxmd.com/read/30481075/role-of-pannexin-and-adenosine-triphosphate-atp-following-myocardial-ischemia-reperfusion
#12
Sarah Brøgger Kristiansen, Gry Freja Skovsted, Lukas Adrian Berchtold, Aneta Radziwon-Balicka, Karin Dreisig, Lars Edvinsson, Majid Sheykhzade, Kristian Agmund Haanes
OBJECTIVES: The purinergic system has not been investigated in detail following ischemia/reperfusion (I/R) injury in the heart. In the present study we focus on both release and response to extracellular adenosine triphosphate (ATP). Pannexin (Panx) channels have been shown to be involved in ATP release from myocytes and can activate P2X1 and P2Y2 receptors on the coronary artery. DESIGN: We applied a well characterized I/R model in rats, with 24 hours of reperfusion...
November 27, 2018: Scandinavian Cardiovascular Journal: SCJ
https://www.readbyqxmd.com/read/30480428/striatal-hippocampal-and-cortical-networks-are-differentially-responsive-to-the-m4-and-m1-muscarinic-acetylcholine-receptor-mediated-effects-of-xanomeline
#13
Catherine A Thorn, Joshua Moon, Clinton A Bourbonais, John Harms, Jeremy R Edgerton, Eda Stark, Stefanus J Steyn, Christopher R Butler, John T Lazzaro, Rebecca E O'Connor, Michael Popiolek
Preclinical and clinical data suggest that muscarinic acetylcholine receptor activation may be therapeutically beneficial for the treatment of schizophrenia and Alzheimer's diseases. This is best exemplified by clinical observations with xanomeline, whose efficacy is thought to be mediated through co-activation of the M1and the M4 muscarinic acetylcholine receptors (mAChRs). Here we examined the impact of treatment with xanomeline and compared it to selective M1 and M4 mAChR activators on in vivo intracellular signaling cascades in mice, including 3'-5'-cyclic adenosine monophosphate-response element binding protein (CREB) phosphorylation and inositol phosphate-1 (IP1) accumulation, in striatum, hippocampus and prefrontal cortex...
November 27, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30478902/glucagon-attenuates-lipid-accumulation-in-cow-hepatocytes-through-ampk-signaling-pathway-activation
#14
Yu Li, Hongyan Ding, Jihong Dong, Sajid Ur Rahman, Shibin Feng, Xichun Wang, Jinjie Wu, Zhe Wang, Guowen Liu, Xiaobing Li, Xinwei Li
The ketotic cows displayed hepatic lipid metabolic disorder and high blood concentration of glucagon. Importantly, adenosine monophosphate-activated protein kinase (AMPK) signaling pathway plays an important role in the hepatic lipid homeostasis. Therefore, the aim of this study was to investigate the effect of glucagon on AMPK pathway and its underlying mechanism on lipid metabolism in cow hepatocytes. Cow hepatocytes were cultured and treated with glucagon and AMPK inhibitor (BML-275). The results showed that glucagon significantly promoted the expression of glucagon receptor and increased the phosphorylation level and activity of AMPKα...
November 27, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30476620/influence-of-incubation-conditions-on-microsomal-metabolism-of-xanthine-derived-a-1-adenosine-receptor-ligands
#15
Daniela Schneider, Dirk Bier, Andreas Bauer, Bernd Neumaier, Marcus Holschbach
INTRODUCTION: In vitro metabolism models such as liver microsomes represent an important tool for the development of novel radioligands. Comparability and physiological relevance of in vitro metabolism data critically depend on the careful evaluation and optimization of assay protocols. We therefore investigated the influence of incubation conditions on the microsomal stability of xanthine-derived A1 adenosine receptor (A1 AR) ligands which have been developed for positron emission tomography (PET)...
November 23, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30473700/atp-and-its-metabolite-adenosine-as-regulators-of-dendritic-cell-activity
#16
REVIEW
Cinthia Silva-Vilches, Sabine Ring, Karsten Mahnke
Adenosine (Ado) is a well-studied neurotransmitter, but it also exerts profound immune regulatory functions. Ado can (i) actively be released by various cells into the tissue environment and can (ii) be produced through the degradation of extracellular ATP by the concerted action of CD39 and CD73. In this sequence of events, the ectoenzyme CD39 degrades ATP into ADP and AMP, respectively, and CD73 catalyzes the last step leading to the production of Ado. Extracellular ATP acts as a "danger" signal and stimulates immune responses, i...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30472151/purinergic-signaling-in-alzheimer-s-disease
#17
REVIEW
Laurie Erb, Lucas T Woods, Mahmoud G Khalafalla, Gary A Weisman
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by three major histopathological markers: amyloid-β (Aβ) plaques, neurofibrillary tangles and gliosis in the central nervous system (CNS). It is now accepted that neuroinflammatory events in the CNS play a crucial role in the development of AD. This review focuses on neuroinflammatory signaling mediated by purinergic receptors (P1 adenosine receptors, P2X ATP-gated ion channels and G protein-coupled P2Y nucleotide receptors) and how therapeutic modulation of purinergic signaling influences disease progression in AD patients and animal models of AD...
November 22, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/30471466/nanobret-ligand-binding-at-a-gpcr-under-endogenous-promotion-facilitated-by-crispr-cas9-genome-editing
#18
Carl W White, Elizabeth K M Johnstone, Heng B See, Kevin D G Pfleger
Bioluminescence resonance energy transfer (BRET) is a versatile tool used to investigate membrane receptor signalling and function. We have recently developed a homogenous NanoBRET ligand binding assay to monitor interactions between G protein-coupled receptors and fluorescent ligands. However, this assay requires the exogenous expression of a receptor fused to the nanoluciferase (Nluc) and is thus not applicable to natively-expressed receptors. To overcome this limitation in HEK293 cells, we have utilised CRISPR/Cas9 genome engineering to insert Nluc in-frame with the endogenous ADORA2B locus this resulted in HEK293 cells expressing adenosine A2B receptors under endogenous promotion tagged on their N-terminus with Nluc...
November 22, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/30471364/adenosine-receptor-agonists-deepen-the-inhibition-of-platelet-aggregation-by-p2y-12-antagonists
#19
Magdalena Boncler, Joanna Wzorek, Nina Wolska, Dawid Polak, Cezary Watala, Marcin Rozalski
Several adenosine receptor (AR) agonists have been shown in the past to possess anti-platelet potential; however, the adjunctive role of AR agonists in anti-platelet therapy with the use of P2Y12 receptor inhibitors has not been elucidated so far. This in vitro aggregation-based study investigates whether the inhibition of platelet function mediated by cangrelor or prasugrel metabolite can be potentiated by AR agonists. It evaluates the effect of non-selective (2-chloroadenosine), A2A -selective (UK 432097, MRE 0094, PSB 0777) and A2B -selective AR agonists (BAY 60-6583) on platelet function in relation to their toxicity, specificity towards adenosine receptor subtypes, structure and solubility...
November 21, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/30471250/functional-gene-expression-of-dopamine-receptors-in-the-male-reproductive-organ-during-sexual-maturation-in-the-honey-bee-apis-mellifera-l
#20
Keisuke Matsushima, Tomohiro Watanabe, Ken Sasaki
Dopamine is a potential integrator between the central nervous system and reproductive system in insects. To test for a possible action of dopamine on the male reproductive organ via hemolymph in honey bees, relative expression levels of dopamine receptor genes and second messenger levels responding to dopamine in the reproductive organ were quantified. Protein content of the three parts of the reproductive organ (testes, seminal vesicles, and mucus glands) differed depending on the age of bees: the protein content of the testes decreased, whereas that of the seminal vesicles and mucus glands increased as males aged...
November 22, 2018: Journal of Insect Physiology
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