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https://www.readbyqxmd.com/read/28088487/adenosine-receptors-and-caffeine-in-retinopathy-of-prematurity
#1
REVIEW
Jiang-Fan Chen, Shuya Zhang, Rong Zhou, Zhenlang Lin, Xiaohong Cai, Jing Lin, Yuqin Huo, Xiaoling Liu
Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants...
January 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28062599/in-vivo-evaluation-of-11c-preladenant-for-pet-imaging-of-adenosine-a2a-receptors-in-the-conscious-monkey
#2
Xiaoyun Zhou, Ronald Boellaard, Kiichi Ishiwata, Muneyuki Sakata, Rudi A Dierckx, Johan de Jong, Shingo Nishiyama, Hiroyuki Ohba, Hideo Tsukada, Erik F de Vries, Philip H Elsinga
: [(11)C]Preladenant was developed as a novel PET ligand for the adenosine A2A receptors (A2ARs). The present study aims to evaluate the suitability of [(11)C]preladenant-PET for the quantification of striatal A2ARs and the assessment of A2AR occupancy in the conscious monkey brain. METHODS: [(11)C]Preladenant was i.v. injected into conscious monkeys (n = 4, 18 PET scans) and a 91-min dynamic scan was started. Arterial blood samples in combination with metabolite analysis were obtained during the scan to provide the input function for kinetic modelling...
January 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28060732/prognostic-impact-of-cd73-and-a2a-adenosine-receptor-expression-in-non-small-cell-lung-cancer
#3
Yusuke Inoue, Katsuhiro Yoshimura, Nobuya Kurabe, Tomoaki Kahyo, Akikazu Kawase, Masayuki Tanahashi, Hiroshi Ogawa, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Hiroshi Niwa, Takafumi Suda, Haruhiko Sugimura
In immune cells, CD73 dephosphorylates and converts extracellular AMP into adenosine, which binds the A2A adenosine receptor (A2AR). Blockade of this interaction, which induces an immunosuppressed niche in the tumor microenvironment, represents a potential novel treatment strategy. The clinical significance of CD73 and A2AR expression in non-small-cell lung cancer (NSCLC), however, has yet to be thoroughly investigated. Here we evaluated CD73 and A2AR protein expression levels using immunohistochemistry in tissue microarrays containing 642 resected NSCLC specimens...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28042771/oxidative-stress-pro-inflammatory-cytokines-and-antioxidants-regulate-expression-levels-of-micrornas-in-parkinson-s-disease
#4
Kedar N Prasad
Parkinson's disease (PD) is a slow progressive neurodegenerative disease associated with abnormal function of extrapyramidal system. Although several biochemical and genetic defects have been identified, increased oxidative stress and chronic inflammation are one of the earliest events that initiate and promote PD. Oxidative stress also participates in impaired non-motor symptoms.The levels of microRNAs that are evolutionarily conserved single-stranded non-coding RNAs of approximately 22 nucleotide in length are altered in PD...
January 2, 2017: Current Aging Science
https://www.readbyqxmd.com/read/28041708/expressions-of-adenosine-a2a-receptors-in-coronary-arteries-and-peripheral-blood-mononuclear-cells-are-correlated-in-coronary-artery-disease-patients
#5
Vlad Gariboldi, Donato Vairo, Régis Guieu, Marion Marlingue, Eléonore Ravis, David Lagier, Alissa Mari, Elsa Thery, Frédéric Collart, Marine Gaudry, Laurent Bonello, Franck Paganelli, Jocelyne Condo, Nathalie Kipson, Emmanuel Fenouillet, Jean Ruf, Giovanna Mottola
BACKGROUND: Altered coronary blood flow occurs in patients with coronary artery disease (CAD). Adenosine strongly impacts blood flow mostly via adenosine A2A receptor (A2AR) expressed in coronary tissues. As part of a systemic regulation of the adenosinergic system, we compared A2AR expression in situ, and on peripheral blood mononuclear cells (PBMC) in CAD patients. METHODS AND RESULTS: Aortic and coronary tissues, and PBMC were sampled in 20 CAD patients undergoing coronary artery bypass surgery and consecutively included...
December 21, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28012867/chronic-oral-administration-of-mpep-an-antagonist-of-mglu5-receptor-during-gestation-and-lactation-alters-mglu5-and-a2a-receptors-in-maternal-and-neonatal-brain
#6
Antonio López-Zapata, David Agustín León-Navarro, María Crespo, José Luis Albasanz, Mairena Martín
Antidepressant and anxiolytic drugs are widely consumed even by pregnant and lactating women. The metabotropic glutamate receptor 5 (mGlu5) antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) exerts antidepressant- and anxiolytic-like actions. Given that treatment for anxiety and depression use to be prolonged in time, it is conceivable a possible modulation of metabotropic glutamate receptors (mGlu receptors) after prolonged MPEP exposure, which could also modify adenosine A2A receptors (A2AR) since functional cross-talk between them has been reported...
December 22, 2016: Neuroscience
https://www.readbyqxmd.com/read/28011152/adenosine-a2a-receptor-stimulation-blocks-development-of-nonalcoholic-steatohepatitis-in-mice-by-multilevel-inhibition-of-signals-that-cause-immunolipotoxicity
#7
Elisa Alchera, Simona Rolla, Chiara Imarisio, Valentina Bardina, Guido Valente, Francesco Novelli, Rita Carini
Lipotoxicity and immunoinflammation are associated with the evolution of steatosis toward nonalcoholic steatohepatitis (NASH). This study reports the ability of adenosine A2a receptor (A2aR) activation to inhibit NASH development by modulating the responses of CD4(+) T-helper (Th) cells to avoid an immuno-mediated potentiation of lipotoxicity. The effect of the A2aR agonist CGS21680 on immunoinflammatory signals, CD4(+)Th cell infiltration and immunolipotoxicity was analyzed in steatotic C57BL/6 mice fed with a methionine-choline-deficient (MCD) diet and in mouse hepatocytes exposed to palmitic acid (PA)...
December 6, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27986907/cutting-edge-adenosine-a2a-receptor-signals-inhibit-germinal-center-t-follicular-helper-cell-differentiation-during-the-primary-response-to-vaccination
#8
Shirdi E Schmiel, Jessica A Yang, Marc K Jenkins, Daniel L Mueller
Adenosine A2a receptor (A2aR) signaling acts as a barrier to autoimmunity by promoting anergy, inducing regulatory T cells, and inhibiting effector T cells. However, in vivo effects of A2aR signaling on polyclonal CD4 T cells during a primary response to foreign Ag has yet to be determined. To address this problem, we immunized mice with peptide Ag 2W1S coupled to PE in CFA and treated with the selective A2aR agonist CGS-21680 (CGS). 2W1S:I-A(b)-specific tetramer-binding CD4 T cells did not become anergic or differentiate into Foxp3(+) regulatory T cells...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27984074/alterations-in-ventral-and-dorsal-striatal-allosteric-a2ar-d2r-receptor-receptor-interactions-after-amphetamine-challenge-relevance-for-schizophrenia
#9
Julia Pintsuk, Dasiel O Borroto-Escuela, Terence K Y Lai, Fang Liu, Kjell Fuxe
Striatal dopamine D2R homodimerization is increased in the dorsal striatum after acute amphetamine challenge and in the amphetamine-induced sensitized state, a well-known animal model of schizophrenia. Therefore, it was tested if the increase in D2R homoreceptor complexes found after acute amphetamine challenge in the saline or the amphetamine sensitized state leads to changes in the antagonistic adenosine A2AR-D2R interactions in the striatum. [(3)H]-raclopride binding was performed in membrane preparations from the ventral and dorsal striatum involving competition with the D2R like agonist quinpirole...
October 29, 2016: Life Sciences
https://www.readbyqxmd.com/read/27975140/profound-hypothermia-after-adenosine-kinase-inhibition-in-a1ar-deficient-mice-suggests-a-receptor-independent-effect-of-intracellular-adenosine
#10
Christoph Eisner, SooMi Kim, Alexandra Grill, Yan Qin, Marion Hoerl, Josephine Briggs, Hayo Castrop, Manfred Thiel, Jurgen Schnermann
Administration of the nucleoside adenosine has been shown to induce hypothermia in a number of species, an effect mediated predominantly by the adenosine 1 receptor (A1AR) subtype. The present experiments were performed to explore the possibility that the rise of intracellular adenosine levels expected to accompany adenosine administration may contribute to the hypothermic effect of adenosine independent of A1AR activation. Since phosphorylation of adenosine by adenosine kinase (ADK) is causal in the maintenance of low intracellular adenosine, we have examined the effect of ADK inhibition on core body temperature (CBT)...
December 14, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27974461/the-gs-protein-coupled-a2a-adenosine-receptor-controls-t-cell-help-in-the-germinal-center
#11
Robert K Abbott, Murillo Silva, Jasmine Labuda, Molly Thayer, Derek W Cain, Phaethon Philbrook, Shalini Sethumadhavan, Stephen Hatfield, Akio Ohta, Michail Sitkovsky
T follicular helper (TFH) cells have been shown to be critically required for the germinal center (GC) reaction where B cells undergo class switch recombination and clonal selection to generate high affinity neutralizing antibodies. However, detailed knowledge of the physiological cues within the GC microenvironment that regulate T cell help is limited. The cAMP elevating, Gs protein coupled A2a adenosine receptor (A2aR) is an evolutionarily conserved receptor that limits and redirects cellular immunity. However, the role of A2aR in humoral immunity and B cell differentiation is unknown...
December 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903722/adenosine-kinase-deficiency-in-the-brain-results-in-maladaptive-synaptic-plasticity
#12
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
#13
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
#14
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
#15
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
#16
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-nonionic-detergents-destabilize-g-protein-coupled-receptors
#17
Sangbae Lee, Allen Mao, Supriyo Bhattacharya, Nathan Robertson, Reinhard Grisshammer, Christopher G Tate, Nagarajan Vaidehi
Stability of detergent-solubilized G-protein-coupled receptors (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...
November 30, 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
#18
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
#19
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
#20
(no author information available yet)
Cotargeting CD73 and A2AR overcomes host-ablated A2AR-induced CD73 expression.
September 30, 2016: Cancer Discovery
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