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https://www.readbyqxmd.com/read/27903722/adenosine-kinase-deficiency-in-the-brain-results-in-maladaptive-synaptic-plasticity
#1
Ursula S Sandau, Mariana Colino-Oliveira, Abbie Jones, Bounmy Saleumvong, Shayla Q Coffman, Long Liu, Catarina Miranda-Lourenço, Cátia Palminha, Vânia L Batalha, Yiming Xu, Yuqing Huo, Maria J Diógenes, Ana M Sebastião, Detlev Boison
: Adenosine kinase (ADK) deficiency in human patients (OMIM:614300) disrupts the methionine cycle and triggers hypermethioninemia, hepatic encephalopathy, cognitive impairment, and seizures. To identify whether this neurological phenotype is intrinsically based on ADK deficiency in the brain or if it is secondary to liver dysfunction, we generated a mouse model with a brain-wide deletion of ADK by introducing a Nestin-Cre transgene into a line of conditional ADK deficient Adk(fl/fl) mice...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27886238/mc5r-and-a2ar-deficiencies-during-experimental-autoimmune-uveitis-identifies-distinct-t-cell-polarization-programs-and-a-biphasic-regulatory-response
#2
Darren J Lee, Janine Preble, Stacey Lee, C Stephen Foster, Andrew W Taylor
Autoantigen-specific regulatory immunity emerges in the spleen of mice recovering from experimental autoimmune uveitis (EAU), a murine model for human autoimmune uveoretinitis. This regulatory immunity provides induced tolerance to ocular autoantigen, and requires melanocortin 5 receptor (MC5r) expression on antigen presenting cells with adenosine 2 A receptor (A2Ar) expression on T cells. During EAU it is not well understood what roles MC5r and A2Ar have on promoting regulatory immunity. Cytokine profile analysis during EAU revealed MC5r and A2Ar each mediate distinct T cell responses, and are responsible for a functional regulatory immune response in the spleen...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872762/understanding-the-functional-plasticity-in-neural-networks-of-the-basal-ganglia-in-cocaine-use-disorder-a-role-for-allosteric-receptor-receptor-interactions-in-a2a-d2-heteroreceptor-complexes
#3
REVIEW
Dasiel O Borroto-Escuela, Karolina Wydra, Julia Pintsuk, Manuel Narvaez, Fidel Corrales, Magdalena Zaniewska, Luigi F Agnati, Rafael Franco, Sergio Tanganelli, Luca Ferraro, Malgorzata Filip, Kjell Fuxe
Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor interactions and hereby induce neural plasticity in the basal ganglia. Studies with A2AR ligands using cocaine self-administration procedures indicate that antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal GABA antireward pathway play a significant role in reducing cocaine induced reward, motivation, and cocaine seeking...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27835671/an-anti-parkinson-s-disease-drug-via-targeting-adenosine-a2a-receptor-enhances-amyloid-%C3%AE-generation-and-%C3%AE-secretase-activity
#4
Jing Lu, Jin Cui, Xiaohang Li, Xin Wang, Yue Zhou, Wenjuan Yang, Ming Chen, Jian Zhao, Gang Pei
γ-secretase mediates the intramembranous proteolysis of amyloid precursor protein (APP) and determines the generation of Aβ which is associated with Alzheimer's disease (AD). Here we identified that an anti-Parkinson's disease drug, Istradefylline, could enhance Aβ generation in various cell lines and primary neuronal cells of APP/PS1 mouse. Moreover, the increased generation of Aβ42 was detected in the cortex of APP/PS1 mouse after chronic treatment with Istradefylline. Istradefylline promoted the activity of γ-secretase which could lead to increased Aβ production...
2016: PloS One
https://www.readbyqxmd.com/read/27807997/adenosine-receptors-expression-in-cardiac-fibroblasts-of-patients-with-left-ventricular-dysfunction-due-to-valvular-disease
#5
Silvia Del Ry, Manuela Cabiati, Veronica Della Latta, Stefania Zimbone, Mariarita Natale, Pietro Enea Lazzerini, Francesco Diciolla, Pier Leopoldo Capecchi, Franco Laghi-Pasini, Maria Aurora Morales
CONTEXT: Adenosine restores tissue homeostasis through the interaction with its membrane receptors (AR) expressed on fibroblasts, endothelial cells, smooth muscle cells and leukocytes, but their modulation is still not fully understood. OBJECTIVE: To evaluate whether changes in the transcriptomic profiling of adenosine receptors (AR) occur in cardiac fibroblasts (CF) of patients (pts) with LV dysfunction due to valvular disease (V). The secondary aim was to compare in the same pts the results obtained at cardiac level with those found in circulating leukocytes...
November 3, 2016: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27792324/how-do-short-chain-non-ionic-detergents-destabilize-gpcrs
#6
Sangbae Lee, Allen Mao, Supriyo Bhattacharya, Nathan Robertson, Reinhard Grisshammer, Christopher G Tate, Nagarajan Vaidehi
Stability of detergent-solubilized GPCRs is crucial for their purification in a biologically relevant state and it is well-known that short chain detergents such as octylglucoside are more denaturing than long chain detergents such as dodecylmaltoside. However, the molecular basis for this phenomenon is poorly understood. To gain insights into the mechanism of detergent destabilization of GPCRs, we used atomistic molecular dynamics simulations of thermostabilized adenosine receptor (A2AR) mutants embedded in either a lipid bilayer or detergent micelles of alkylmaltosides and alkylglucosides...
October 28, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27789720/preclinical-evaluation-and-quantification-of-18f-fluoroethyl-and-18f-fluoropropyl-analogs-of-sch442416-as-radioligands-for-pet-imaging-of-the-adenosine-a2a-receptors-in-rat-brain
#7
Shivashankar Khanapur, Aren van Waarde, Rudi A Dierckx, Philip H Elsinga, Michel Koole
: Cerebral adenosine A2A receptors (A2ARs) are attractive therapeutic targets for neuropsychiatric disorders. (18)F-Fluoroethyl and (18)F-fluoropropyl analogs of SCH442416 ((18)F-FESCH and (18)F-FPSCH) were developed as A2AR specific PET ligands. Aim is to determine an appropriate compartmental model for tracer kinetics, evaluate a reference tissue approach and select the most suitable PET ligand. METHODS: A 90 min dynamic PET with arterial blood sampling and metabolite analysis was acquired for 22 healthy male Wistar rats starting at (18)F-FESCH (n = 12) and (18)F-FPSCH (n = 10) injection...
October 27, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27696085/transcriptomic-effects-of-adenosine-2a-receptor-deletion-in-healthy-and-endotoxemic-murine-myocardium
#8
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
September 30, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27694381/coinhibition-of-adenosine-signaling-nodes-enhances-antitumor-immunity
#9
(no author information available yet)
Cotargeting CD73 and A2AR overcomes host-ablated A2AR-induced CD73 expression.
September 30, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27663541/caffeine-alters-glutamate-aspartate-transporter-function-and-expression-in-rat-retina
#10
Adriana Pinto de Freitas, Danielle Dias Pinto Ferreira, Arlete Fernandes, Robertta Silva Martins, Vladimir Pedro Peralva Borges-Martins, Matheus Figueiredo Sathler, Maurício Dos-Santos-Pereira, Roberto Paes-de-Carvalho, Elizabeth Giestal-de-Araujo, Ricardo Augusto de Melo Reis, Regina Celia Cussa Kubrusly
l-Glutamate and l-aspartate are the main excitatory amino acids (EAAs) in the Central Nervous System (CNS) and their uptake regulation is critical for the maintenance of the excitatory balance. Excitatory amino acid transporters (EAATs) are widely distributed among central neurons and glial cells. GLAST and GLT1 are expressed in glial cells, whereas excitatory amino acid transporter 3/excitatory amino acid carrier 1 (EAAT3/EAAC1) is neuronal. Different signaling pathways regulate glutamate uptake by modifying the activity and expression of EAATs...
September 20, 2016: Neuroscience
https://www.readbyqxmd.com/read/27658704/baicalin-attenuates-bleomycin-induced-pulmonary-fibrosis-via-adenosine-a2a-receptor-related-tgf-%C3%AE-1-induced-erk1-2-signaling-pathway
#11
Xiaoying Huang, Yicheng He, Yanfan Chen, Peiliang Wu, Di Gui, Hui Cai, Ali Chen, Mayun Chen, Caijun Dai, Dan Yao, Liangxing Wang
BACKGROUND: Baicalin has been reported to have anti-fibrosis effect; however, its mechanism still remains to be elucidated. Adenosine A2a receptor (A2aR) is a novel inflammation regulator, and transforming growth factor-β1 (TGF-β1)-induced extracellular signal regulated kinase1/2 (ERK1/2) signaling pathway plays an important role in idiopathic pulmonary fibrosis (IPF). This study was to explore the relationship of A2aR and TGF-β1-induced ERK1/2 in bleomycin (BLM)-induced pulmonary fibrosis in mice, and to investigate whether A2aR mediate the anti-fibrosis effect of Baicalin on BLM-induced pulmonary fibrosis...
2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27647162/activation-of-adenosine-2a-receptor-inhibits-neutrophil-apoptosis-in-an-autophagy-dependent-manner-in-mice-with-systemic-inflammatory-response-syndrome
#12
Yang-Wuyue Liu, Ting Yang, Li Zhao, Zhenhong Ni, Nan Yang, Fengtian He, Shuang-Shuang Dai
Systemic inflammatory response syndrome (SIRS) is an overwhelming whole body inflammation caused by infectious diseases or sterile insults. Neutrophils are the dominant participants during inflammation, and their survival and death determine the initiation as well as resolution of SIRS. Apoptosis and autophagy are two fundamental cellular processes that modulating cell fate, but their correlation and regulators in neutrophils under SIRS condition have not been elucidated. In this study, we demonstrated that high dose of LPS induced both apoptosis and autophagy of neutrophils in a mouse SIRS model and LPS-stimulated neutrophils in vitro...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27622332/co-inhibition-of-cd73-and-a2ar-adenosine-signaling-improves-anti-tumor-immune-responses
#13
Arabella Young, Shin Foong Ngiow, Deborah S Barkauskas, Erin Sult, Carl Hay, Stephen J Blake, Qihui Huang, Jing Liu, Kazuyoshi Takeda, Michele W L Teng, Kris Sachsenmeier, Mark J Smyth
Preclinical studies targeting the adenosinergic pathway have gained much attention for their clinical potential in overcoming tumor-induced immunosuppression. Here, we have identified that co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor (A2AR) that mediates adenosine signaling in leuokocytes, by using compound gene-targeted mice or therapeutics that target these molecules, limits tumor initiation, growth, and metastasis. This tumor control requires effector lymphocytes and interferon-γ, while antibodies targeting CD73 promote an optimal therapeutic response in vivo when engaging activating Fc receptors...
September 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27622328/co-targeting-of-adenosine-signaling-pathways-for-immunotherapy-potentiation-by-fc-receptor-engagement
#14
Rony Dahan, Jeffrey V Ravetch
Targeting the signaling pathway of the immunosuppressive metabolite adenosine is an emerging approach for cancer immunotherapy. In this issue of Cancer Cell, Young et al. describe that co-inhibition of the adenosingenic pathway through blockade of both CD73 and A2AR enhances antitumor efficacy through distinct mechanisms.
September 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27600688/adenosine-receptors-as-markers-of-brain-iron-deficiency-implications-for-restless-legs-syndrome
#15
César Quiroz, Seema Gulyani, Wan Ruiqian, Jordi Bonaventura, Roy Cutler, Virginia Pearson, Richard P Allen, Christopher J Earley, Mark P Mattson, Sergi Ferré
Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyperarousal and sleep disturbances in Restless Legs Syndrome (RLS) constitute two pathophysiologically distinct but interrelated clinical phenomena, which seem to depend mostly on alterations in dopaminergic and glutamatergic neurotransmission, respectively. Brain iron deficiency is considered as a main pathogenetic mechanism in RLS. Rodents with brain iron deficiency represent a valuable pathophysiological model of RLS, although they do not display motor disturbances...
December 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27590504/activation-of-the-a2b-adenosine-receptor-in-b16-melanomas-induces-cxcl12-expression-in-fap-positive-tumor-stromal-cells-enhancing-tumor-progression
#16
Claudia Sorrentino, Lucio Miele, Amalia Porta, Aldo Pinto, Silvana Morello
The A2B receptor (A2BR) can mediate adenosine-induced tumor proliferation, immunosuppression and angiogenesis. Targeting the A2BR has proved to be therapeutically effective in some murine tumor models, but the mechanisms of these effects are still incompletely understood. Here, we report that pharmacologic inhibition of A2BR with PSB1115, which inhibits tumor growth, decreased the number of fibroblast activation protein (FAP)-expressing cells in tumors in a mouse model of melanoma. This effect was associated with reduced expression of fibroblast growth factor (FGF)-2...
August 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27577981/a2ar-binding-kinetics-in-the-ligand-depletion-regime
#17
Patrick M McNeely, Andrea N Naranjo, Kimberly Forsten-Williams, Anne Skaja Robinson
Ligand binding plays a fundamental role in stimulating the downstream signaling of membrane receptors. Here, ligand-binding kinetics of the full-length human adenosine A2A receptor (A2AR) reconstituted in detergent micelles were measured using a fluorescently labeled ligand via fluorescence anisotropy. Importantly, to optimize the signal-to-noise ratio, these experiments were conducted in the ligand depletion regime. In the ligand depletion regime, the assumptions used to determine analytical solutions for one-site binding models for either one or two ligands in competition are no longer valid...
August 30, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27570825/gpr88-in-a2ar-neurons-enhances-anxiety-like-behaviors
#18
Aura Carole Meirsman, Anne Robé, Alban de Kerchove d'Exaerde, Brigitte Lina Kieffer
GPR88 is an orphan G-protein-coupled receptor highly expressed in striatal dopamine D1 (receptor) R- and D2R-expressing medium spiny neurons. This receptor is involved in activity and motor responses, and we previously showed that this receptor also regulates anxiety-like behaviors. To determine whether GPR88 in D2R-expressing neurons contributes to this emotional phenotype, we generated conditional Gpr88 knock-out mice using adenosine A2AR (A2AR)-Cre-driven recombination, and compared anxiety-related responses in both total and A2AR-Gpr88 KO mice...
July 2016: ENeuro
https://www.readbyqxmd.com/read/27567601/equilibrative-nucleoside-transporter-ent1-as-a-biomarker-of-huntington-disease
#19
Xavier Guitart, Jordi Bonaventura, William Rea, Marco Orrú, Lucrezia Cellai, Ilaria Dettori, Felicita Pedata, Marc Brugarolas, Antonio Cortés, Vicent Casadó, Ching-Pang Chang, Manikandan Narayanan, Yijuang Chern, Sergi Ferré
The initial goal of this study was to investigate alterations in adenosine A2A receptor (A2AR) density or function in a rat model of Huntington disease (HD) with reported insensitivity to an A2AR antagonist. Unsuspected negative results led to the hypothesis of a low striatal adenosine tone and to the search for the mechanisms involved. Extracellular striatal concentrations of adenosine were measured with in vivo microdialysis in two rodent models of early neuropathological stages of HD disease, the Tg51 rat and the zQ175 knock-in mouse...
December 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27520357/macrophage-a2a-adenosine-receptors-are-essential-to-protect-from-progressive-kidney-injury
#20
Luan D Truong, Jessica Trostel, Rachel McMahan, Jiang-Fan Chen, Gabriela E Garcia
A2A adenosine receptors (A2ARs) are endogenous inhibitor of inflammation. Macrophages that are key effectors of kidney disease progression express A2ARs. We investigated the role of A2ARs in kidney inflammation in a macrophage-mediated anti-glomerular basement membrane reactive serum-induced immune nephritis in A2AR-deficient mice. Sub-threshold doses of glomerular basement membrane-reactive serum induced more severe and prolonged kidney damage with higher levels of proinflammatory cytokines and greater accumulation of inflammatory cells in A2AR(-/-) mice than wild-type (WT) mice...
October 2016: American Journal of Pathology
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