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adenosine a2a receptor

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https://www.readbyqxmd.com/read/28338619/role-and-function-of-a2a-and-a%C3%A2-adenosine-receptors-in-patients-with-ankylosing-spondylitis-psoriatic-arthritis-and-rheumatoid-arthritis
#1
Annalisa Ravani, Fabrizio Vincenzi, Alessandra Bortoluzzi, Melissa Padovan, Silvia Pasquini, Stefania Gessi, Stefania Merighi, Pier Andrea Borea, Marcello Govoni, Katia Varani
Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory rheumatic diseases that affect joints, causing debilitating pain and disability. Adenosine receptors (ARs) play a key role in the mechanism of inflammation, and the activation of A2A and A₃AR subtypes is often associated with a reduction of the inflammatory status. The aim of this study was to investigate the involvement of ARs in patients suffering from early-RA (ERA), RA, AS and PsA. Messenger RNA (mRNA) analysis and saturation binding experiments indicated an upregulation of A2A and A₃ARs in lymphocytes obtained from patients when compared with healthy subjects...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28337995/cigarette-smoke-impairs-a2a-adenosine-receptor-mediated-wound-repair-through-up-regulation-of-duox-1-expression
#2
Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A Wyatt, Kusum Kharbanda, Samantha Simet Chadwick, Narasaiah Kolliputi, Diane S Allen-Gipson
Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335379/the-role-of-adenosine-signaling-in-headache-a-review
#3
REVIEW
Nathan T Fried, Melanie B Elliott, Michael L Oshinsky
Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments...
March 13, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28317879/a-novel-method-for-screening-adenosine-receptor-specific-agonists-for-use-in-adenosine-drug-development
#4
Karlie R Jones, Uimook Choi, Ji-Liang Gao, Robert D Thompson, Larry E Rodman, Harry L Malech, Elizabeth M Kang
Agonists that target the A1, A2A, A2B and A3 adenosine receptors have potential to be potent treatment options for a number of diseases, including autoimmune diseases, cardiovascular disease and cancer. Because each of these adenosine receptors plays a distinct role throughout the body, obtaining highly specific receptor agonists is essential. Of these receptors, the adenosine A2AR and A2BR share many sequence and structural similarities but highly differ in their responses to inflammatory stimuli. Our laboratory, using a combination of specially developed cell lines and calcium release analysis hardware, has created a new and faster method for determining specificity of synthetic adenosine agonist compounds for the A2A and A2B receptors in human cells...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28304243/retinal-a2a-and-a3-adenosine-receptors-modulate-the-components-of-the-rat-electroretinogram
#5
Gudmundur Jonsson, Thor Eysteinsson
Adenosine is a neuromodulator present in various areas of the central nervous system, including the retina. Adenosine may serve a neuroprotective role in the retina, based on electroretinogram (ERG) recordings from the rat retina. Our purpose was to assess the role of A2A and A3 adenosine receptors in the generation and modulation of the rat ERG. The flash ERG was recorded with corneal electrodes from Sprague Dawley rats. Agonists and antagonists for A2A and A3 receptors, and adenosine were injected (5 µl) into the vitreous...
January 2017: Visual Neuroscience
https://www.readbyqxmd.com/read/28300546/cocaine-self-administration-specifically-increases-a2ar-d2r-and-d2r-sigma1r-heteroreceptor-complexes-in-the-rat-nucleus-accumbens-shell-relevance-for-cocaine-use-disorder
#6
Dasiel O Borroto-Escuela, Manuel Narváez, Karolina Wydra, Julia Pintsuk, Luca Pinton, Antonio Jimenez-Beristain, Michael Di Palma, Joanna Jastrzębska, Malgorzata Filip, Kjell Fuxe
Adenosine 2A receptor (A2AR) agonists were indicated to reduce cocaine reward and cocaine seeking mainly through activation of antagonistic allosteric A2AR-dopamine D2R (D2R) interactions in A2AR-D2R heteroreceptor complexes. Furthermore, it was shown that modulation of cocaine reward involves antagonistic A2AR-D2R interactions in the ventral but not the dorsal striatum in rats. In the current work the proximity ligation assay (PLA) was used to further study the A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell and core as well as the dorsal striatum under the influence of cocaine self-administration in rats...
March 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28295154/phenotypical-analysis-of-ectoenzymes-cd39-cd73-and-adenosine-receptor-2a-in-cd4-cd25-high-foxp3-regulatory-t-cells-in-psoriasis
#7
Ling Han, Hideaki Sugiyama, Qi Zhang, Kexiang Yan, Xu Fang, Thomas S McCormick, Kevin D Cooper, Qiong Huang
BACKGROUND: CD39 and CD73 are two novel cell surface markers of CD25(high) Foxp3(+) regulatory T-cells (Tregs). Concordant expression of these two ectoenzymes not only discriminate Tregs from other cell populations, but also generates pericellular adenosine, which has been reported to suppress proliferation of activated T effector (Teff) cells. Because it is currently unclear whether human ectoenzymes (CD39/CD73) are involved in the impaired suppressive activity of Tregs in psoriasis, we examined the frequencies and phenotypes of CD39/CD73-expressing Tregs and related receptor adenosine receptor 2A (A2A R) in peripheral blood of patients with different types of psoriasis...
March 15, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28294142/inosine-attenuates-spontaneous-activity-in-the-rat-neurogenic-bladder-through-an-a2b-pathway
#8
Claire Doyle, Vivian Cristofaro, Bryan S Sack, Stefan N Lukianov, Mattias Schäfer, Yeun Goo Chung, Maryrose P Sullivan, Rosalyn M Adam
Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293100/adenosine-a2a-receptor-agonist-prevents-cardiac-remodeling-and-dysfunction-in-spontaneously-hypertensive-male-rats-after-myocardial-infarction
#9
Jaqueline S da Silva, Daniele Gabriel-Costa, Roberto T Sudo, Hao Wang, Leanne Groban, Emanuele B Ferraz, José Hamilton M Nascimento, Carlos Alberto M Fraga, Eliezer J Barreiro, Gisele Zapata-Sudo
BACKGROUND: This work evaluated the hypothesis that 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294), an agonist of adenosine A2A receptor, could be beneficial for preventing cardiac dysfunction due to hypertension associated with myocardial infarction (MI). METHODS: Male spontaneously hypertensive rats (SHR) were randomly divided into four groups (six animals per group): sham-operation (SHR-Sham), and myocardial infarction rats (SHR-MI) were treated orally either with vehicle or LASSBio-294 (10 and 20 mg...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28287473/structural-probing-and-molecular-modeling-of-the-a%C3%A2-adenosine-receptor-a-focus-on-agonist-binding
#10
REVIEW
Antonella Ciancetta, Kenneth A Jacobson
Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A₁, A2A, A2B and A₃, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A₃AR (hA₃AR) subtype is implicated in several cytoprotective functions. Therefore, hA₃AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. Structure-based molecular modeling techniques have been applied over the years to rationalize the structure-activity relationships (SARs) of newly emerged A₃AR ligands, guide the subsequent lead optimization, and interpret site-directed mutagenesis (SDM) data from a molecular perspective...
March 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28266889/lung-injury-pathways-adenosine-receptor-2b-signaling-limits-development-of-ischemic-bronchiolitis-obliterans-organizing-pneumonia
#11
John C Densmore, Terry R Schaid, Paul M Jeziorczak, Meetha Medhora, Said Audi, Shraddha Nayak, John Auchampach, Melinda R Dwinell, Aron M Geurts, Elizabeth R Jacobs
Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. MATERIALS AND METHODS: Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC...
March 7, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28264466/synthesis-and-characterization-of-a-new-bivalent-ligand-combining-caffeine-and-docosahexaenoic-acid
#12
Víctor Fernández-Dueñas, Jhonny Azuaje, Xavier Morató, Begoña Cordobilla, Joan Carles Domingo, Eddy Sotelo, Francisco Ciruela
Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson's disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine...
February 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28263576/in-situ-reconstitution-of-the-adenosine-a2a-receptor-in-spontaneously-formed-synthetic-liposomes
#13
Roberto J Brea, Christian M Cole, Brent R Lyda, Libin Ye, R Scott Prosser, Roger K Sunahara, Neal K Devaraj
Cell transmembrane receptors play a key role in the detection of environmental stimuli and control of intracellular communication. G protein-coupled receptors constitute the largest transmembrane protein family involved in cell signaling. However, current methods for their functional reconstitution in biomimetic membranes remain both challenging and limited in scope. Herein, we describe the spontaneous reconstitution of adenosine A2A receptor (A2AR) during the de novo formation of synthetic liposomes via native chemical ligation...
March 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28255202/adenosine-receptors-as-a-biological-pathway-for-the-anti-inflammatory-and-beneficial-effects-of-low-frequency-low-energy-pulsed-electromagnetic-fields
#14
REVIEW
Katia Varani, Fabrizio Vincenzi, Annalisa Ravani, Silvia Pasquini, Stefania Merighi, Stefania Gessi, Stefania Setti, Matteo Cadossi, Pier Andrea Borea, Ruggero Cadossi
Several studies explored the biological effects of low frequency low energy pulsed electromagnetic fields (PEMFs) on human body reporting different functional changes. Much research activity has focused on the mechanisms of interaction between PEMFs and membrane receptors such as the involvement of adenosine receptors (ARs). In particular, PEMF exposure mediates a significant upregulation of A2A and A3ARs expressed in various cells or tissues involving a reduction in most of the proinflammatory cytokines. Of particular interest is the observation that PEMFs, acting as modulators of adenosine, are able to increase the functionality of the endogenous agonist...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28252203/pathologic-overproduction-the-bad-side-of-adenosine
#15
REVIEW
Pier Andrea Borea, Stefania Gessi, Stefania Merighi, Fabrizio Vincenzi, Katia Varani
Adenosine is an endogenous ubiquitous purine nucleoside, increased by hypoxia, ischemia and tissue damage that mediates a number of physiopathological effects by interacting with four G-protein-coupled receptors, identified as A1 , A2A , A2B , and A3 . Physiological and acutely-increased adenosine is associated with beneficial effects mostly including vasodilation and decrease of inflammation. In contrast chronic overproduction of adenosine occurs in important pathological states, where long lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage...
March 2, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28251649/evidence-for-purine-nucleoside-phosphorylase-pnp-release-from-rat-c6-glioma-cells
#16
Patricia Giuliani, Mariachiara Zuccarini, Silvana Buccella, Luis Emiliano Peña-Altamira, Elisabetta Polazzi, Marco Virgili, Barbara Monti, Alessandro Poli, Michel P Rathbone, Patrizia Di Iorio, Renata Ciccarelli, Francesco Caciagli
Intracellular purine turnover is mainly oriented to preserving the level of triphosphate nucleotides, fundamental molecules in vital cell functions that, when released outside cells, act as receptor signals. Conversely, high levels of purine bases and uric acid are found in the extracellular milieu, even in resting conditions. These compounds could derive from nucleosides/bases that, having escaped to cell reuptake, are metabolized by extracellular enzymes similar to the cytosolic ones. Focusing on purine nucleoside phosphorylase (PNP) that catalyzes the reversible phosphorolysis of purine (deoxy)-nucleosides/bases, we found that it is constitutively released from cultured rat C6 glioma cells into the medium, and has a molecular weight and enzyme activity similar to the cytosolic enzyme...
March 2, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28250576/having-a-coffee-break-the-impact-of-caffeine-consumption-on-microglia-mediated-inflammation-in-neurodegenerative-diseases
#17
REVIEW
Maria H Madeira, Raquel Boia, António F Ambrósio, Ana R Santiago
Caffeine is the major component of coffee and the most consumed psychostimulant in the world and at nontoxic doses acts as a nonselective adenosine receptor antagonist. Epidemiological evidence suggests that caffeine consumption reduces the risk of several neurological and neurodegenerative diseases. However, despite the beneficial effects of caffeine consumption in human health and behaviour, the mechanisms by which it impacts the pathophysiology of neurodegenerative diseases still remain to be clarified. A promising hypothesis is that caffeine controls microglia-mediated neuroinflammatory response associated with the majority of neurodegenerative conditions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28239340/dopamine-induced-changes-in-g%C3%AE-olf-protein-levels-in-striatonigral-and-striatopallidal-medium-spiny-neurons-underlie-the-genesis-of-l-dopa-induced-dyskinesia-in-parkinsonian-mice
#18
Ryoma Morigaki, Shinya Okita, Satoshi Goto
The dopamine precursor, l-3,4-dihydroxyphenylalanine (l-DOPA), exerts powerful therapeutic effects but eventually generates l-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD). LID has a close link with deregulation of striatal dopamine/cAMP signaling, which is integrated by medium spiny neurons (MSNs). Olfactory type G-protein α subunit (Gαolf), a stimulatory GTP-binding protein encoded by the GNAL gene, is highly concentrated in the striatum, where it positively couples with dopamine D1 (D1R) receptor and adenosine A2A receptor (A2AR) to increase intracellular cAMP levels in MSNs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28235548/chronic-and-acute-adenosine-a2a-receptor-blockade-prevents-long-term-episodic-memory-disruption-caused-by-acute-cannabinoid-cb1-receptor-activation
#19
Francisco M Mouro, Vânia L Batalha, Diana G Ferreira, Joana E Coelho, Younis Baqi, Christa E Müller, Luísa V Lopes, Joaquim A Ribeiro, Ana M Sebastião
Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB1 receptor (CB1R)-induced memory deficits through an adenosine A1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A2A receptors (A2ARs) affects long-term episodic memory deficits induced by a single injection of a selective CB1R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i...
February 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28220900/membrane-cholesterol-access-into-a-g-protein-coupled-receptor
#20
Ramon Guixà-González, José L Albasanz, Ismael Rodriguez-Espigares, Manuel Pastor, Ferran Sanz, Maria Martí-Solano, Moutusi Manna, Hector Martinez-Seara, Peter W Hildebrand, Mairena Martín, Jana Selent
Cholesterol is a key component of cell membranes with a proven modulatory role on the function and ligand-binding properties of G-protein-coupled receptors (GPCRs). Crystal structures of prototypical GPCRs such as the adenosine A2A receptor (A2AR) have confirmed that cholesterol finds stable binding sites at the receptor surface suggesting an allosteric role of this lipid. Here we combine experimental and computational approaches to show that cholesterol can spontaneously enter the A2AR-binding pocket from the membrane milieu using the same portal gate previously suggested for opsin ligands...
February 21, 2017: Nature Communications
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