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Journal articles on the topic 'A2a'

Author: Grafiati

Published: 4 June 2021

Last updated: 27 April 2022

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1

Kusano, Yoshikazu, German Echeverry, Greg Miekisiak, et al. "Role of Adenosine A2 Receptors in Regulation of Cerebral Blood Flow during Induced Hypotension." Journal of Cerebral Blood Flow & Metabolism 30, no. 4 (2009): 808–15. http://dx.doi.org/10.1038/jcbfm.2009.244.

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The mechanisms responsible for vascular autoregulation in the brain during changes in mean arterial blood pressure are ambiguous. Potentially, adenosine, a purine nucleoside and potent vasodilator, may be involved as earlier studies have documented an increase in brain adenosine concentrations with cerebral ischemia and hypotension. Consequently, we tested the hypothesis that adenosine is involved in vasodilatation during hypotension within the autoregulatory range (>50 mm Hg) by exposing adenosine 2a receptor (A2aR) knockout and wild type (WT) mice to short (2 to 5 mins) periods of hypoten

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Wolska, Nina, and Marcin Rozalski. "Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy." International Journal of Molecular Sciences 20, no. 21 (2019): 5475. http://dx.doi.org/10.3390/ijms20215475.

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Adenosine receptors are a subfamily of highly-conserved G-protein coupled receptors. They are found in the membranes of various human cells and play many physiological functions. Blood platelets express two (A2A and A2B) of the four known adenosine receptor subtypes (A1, A2A, A2B, and A3). Agonization of these receptors results in an enhanced intracellular cAMP and the inhibition of platelet activation and aggregation. Therefore, adenosine receptors A2A and A2B could be targets for anti-platelet therapy, especially under circumstances when classic therapy based on antagonizing the purinergic r

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Sharifi-Sanjani, Maryam, Xueping Zhou, Shinichi Asano, et al. "Interactions between A2A adenosine receptors, hydrogen peroxide, and KATP channels in coronary reactive hyperemia." American Journal of Physiology-Heart and Circulatory Physiology 304, no. 10 (2013): H1294—H1301. http://dx.doi.org/10.1152/ajpheart.00637.2012.

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Myocardial metabolites such as adenosine mediate reactive hyperemia, in part, by activating ATP-dependent K+ (KATP) channels in coronary smooth muscle. In this study, we investigated the role of adenosine A2A and A2B receptors and their signaling mechanisms in reactive hyperemia. We hypothesized that coronary reactive hyperemia involves A2A receptors, hydrogen peroxide (H2O2), and KATP channels. We used A2A and A2B knockout (KO) and A2A/2B double KO (DKO) mouse hearts for Langendorff experiments. Flow debt for a 15-s occlusion was repaid 128 ± 8% in hearts from wild-type (WT) mice; this was re

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Zheng, Yanying, Li Liu, Yi Sun, et al. "Comparative Polymorphism of BAT-26 between Healthy Individuals and Cancer Patients and Its Cancer Risk Implication for Local Chinese." International Journal of Biological Markers 31, no. 3 (2016): 252–57. http://dx.doi.org/10.5301/jbm.5000179.

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Purpose BAT-26 is one of the representative markers for microsatellite instability evaluation and presents different polymorphisms in different ethnic populations. The current knowledge of its comparative polymorphism between healthy individuals and cancer patients in the Chinese population is insufficient. This study aims to analyze germline polymorphic variations of BAT-26 between healthy individuals and cancer patients in Chinese from Jiangsu province and the associated cancer risk implications. Methods The various BAT-26 alleles and their percentages in cervical cells from 500 healthy wome

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Nao, Naganori, Miwako Saikusa, Ko Sato, et al. "Recent Molecular Evolution of Human Metapneumovirus (HMPV): Subdivision of HMPV A2b Strains." Microorganisms 8, no. 9 (2020): 1280. http://dx.doi.org/10.3390/microorganisms8091280.

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Human metapneumovirus (HMPV) is a major etiological agent of acute respiratory infections in humans. HMPV has been circulating worldwide for more than six decades and is currently divided into five agreed-upon subtypes: A1, A2a, A2b, B1, and B2. Recently, the novel HMPV subtypes A2c, A2b1, and A2b2 have been proposed. However, the phylogenetic and evolutionary relationships between these recently proposed HMPV subtypes are unclear. Here, we report a genome-wide phylogenetic and evolutionary analysis of 161 HMPV strains, including unique HMPV subtype A2b strains with a 180- or 111-nucleotide du

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Gebremedhin, Debebe, Brian Weinberger, David Lourim, and David R. Harder. "Adenosine Can Mediate its Actions through Generation of Reactive Oxygen Species." Journal of Cerebral Blood Flow & Metabolism 30, no. 10 (2010): 1777–90. http://dx.doi.org/10.1038/jcbfm.2010.70.

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Adenosine is an important cerebral vasodilator, but mediating mechanisms are not understood. We investigated the expression of adenosine receptor subtypes in isolated cerebral arterial muscle cells (CAMCs), and their role in adenosine-induced superoxide (O2−) generation and reduction in cerebral arterial tone. Reverse transcriptase-PCR, western blotting, and immunofluorescence studies have shown that CAMCs express transcript and protein for A1, A2A, A2B, and A3 adenosine receptors. Stimulation of CAMCs with adenosine or the A2A agonist CGS-21680 increased the generation of O2− that was attenua

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Chen, Yinghong, Sara Epperson, Lala Makhsudova, et al. "Functional effects of enhancing or silencing adenosine A2b receptors in cardiac fibroblasts." American Journal of Physiology-Heart and Circulatory Physiology 287, no. 6 (2004): H2478—H2486. http://dx.doi.org/10.1152/ajpheart.00217.2004.

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Cardiac fibroblasts (CF) express adenosine (ADO) receptors, and pharmacological evidence suggests the possible involvement of the A2 (A2a and A2b) receptor (A2aR and A2bR) subtypes in inhibiting cell functions involved in fibrosis. The main objective of this study was to define the contributions of A2a and/or A2b receptors in modulating ADO-induced decreases in CF functions. For this purpose, CF were either treated pharmacologically or had the A2aR or A2bR levels modified through the use of recombinant adenovirus or siRNA. The assessment of mRNA expression in adult rat CF yielded evidence for

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ARMSTRONG, John M., Jiang Fan CHEN, Michael A. SCHWARZSCHILD, et al. "Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene-deficient mice." Biochemical Journal 354, no. 1 (2001): 123–30. http://dx.doi.org/10.1042/bj3540123.

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Agonist binding to extracellular A2A adenosine receptors (A2ARs) inhibits the activation of virtually all tested functions of T-cells and can induce apoptosis in thymocytes. The evaluation of levels of expression of these immunosuppressive receptors is expected to clarify whether the absence of spare A2ARs (no ‘receptor reserve’) might be one of the mechanisms of attenuation of the effects of extracellular adenosine on T-cells. A2A transcript is found in T-cells and functional receptors can be demonstrated, but the density of receptor on T-cells is too low to be detected by radioligand binding

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Gündel, Daniel, Thu Hang Lai, Sladjana Dukic-Stefanovic, et al. "Non-Invasive Assessment of Locally Overexpressed Human Adenosine 2A Receptors in the Heart of Transgenic Mice." International Journal of Molecular Sciences 23, no. 3 (2022): 1025. http://dx.doi.org/10.3390/ijms23031025.

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A2A adenosine receptors (A2A-AR) have a cardio-protective function upon ischemia and reperfusion, but on the other hand, their stimulation could lead to arrhythmias. Our aim was to investigate the potential use of the PET radiotracer [18F]FLUDA to non-invasively determine the A2A-AR availability for diagnosis of the A2AR status. Therefore, we compared mice with cardiomyocyte-specific overexpression of the human A2A-AR (A2A-AR TG) with the respective wild type (WT). We determined: (1) the functional impact of the selective A2AR ligand FLUDA on the contractile function of atrial mouse samples, (

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Franco, Rafael, Rafael Rivas-Santisteban, Gemma Navarro, and Irene Reyes-Resina. "Adenosine Receptor Antagonists to Combat Cancer and to Boost Anti-Cancer Chemotherapy and Immunotherapy." Cells 10, no. 11 (2021): 2831. http://dx.doi.org/10.3390/cells10112831.

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Extracellular adenosine accumulates in the environment of numerous tumors. For years, this fact has fueled preclinical research to determine whether adenosine receptors (ARs) could be the target to fight cancer. The four ARs discovered so far, A1, A2A, A2B and A3, belong to the class A family of G protein-coupled receptors (GPCRs) and all four have been involved in one way or another in regulating tumor progression. Prompted by the successful anti-cancer immunotherapy, the focus was placed on the ARs more involved in regulation of immune cell differentiation and activation and that are able to

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Lillo, Alejandro, Iu Raïch, Jaume Lillo, Catalina Pérez-Olives, Gemma Navarro, and Rafael Franco. "Expression of the Adenosine A2A-A3 Receptor Heteromer in Different Brain Regions and Marked Upregulation in the Microglia of the Transgenic APPSw,Ind Alzheimer’s Disease Model." Biomedicines 10, no. 2 (2022): 214. http://dx.doi.org/10.3390/biomedicines10020214.

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Adenosine (Ado) receptors have been instrumental in the detection of heteromers and other higher-order receptor structures, mainly via interactions with other cell surface G-protein-coupled receptors. Apart from the first report of the A1 Ado receptor interacting with the A2A Ado receptor, there has been more recent data on the possibility that every Ado receptor type, A1, A2A, A2B, and A3, may interact with each other. The aim of this paper was to look for the expression and function of the A2A/A3 receptor heteromer (A2AA3Het) in neurons and microglia. In situ proximity ligation assays (PLA),

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Teng, Bunyan, Daniel N. Darlington, and Andrew P. Cap. "Adenosine Receptor Identification for Controlling Platelet Aggregation." Blood 132, Supplement 1 (2018): 3733. http://dx.doi.org/10.1182/blood-2018-99-116213.

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Abstract Introduction: Adenosine, an autacoid and metabolite of ATP, has been known to have anti-platelet properties. Of the 4 adenosine receptors, both A2A and/or A2B have been implicated in adenosine-mediated anti-platelet properties, while the roles of A1 and A3 have not been clearly defined in humans. In addition, previous studies show that A2A/A2B on platelets are G-Protein Coupled Receptors and are coupled to a stimulatory G-protein that activate adenylyl cyclase and subsequently increase intracellular cAMP. An elevation of cAMP in platelets inhibits aggregation. In this study, we set ou

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Darlington, Daniel N., Xiaowu Wu, Kevin L. Chang, James Bynum, and Andrew P. Cap. "Regulation of Platelet Function By Adenosine Receptors." Blood 134, Supplement_1 (2019): 2348. http://dx.doi.org/10.1182/blood-2019-131129.

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Introduction: We have recently shown that severe trauma and hemorrhage lead to inhibition of platelet aggregation and an elevation in cyclic adenosine monophosphate (cAMP). Adenosine is one of the few humoral agents known to stimulate cAMP in platelets. Because adenosine is released from damaged tissue, it may contribute to the platelet dysfunction seen after severe trauma. Platelets have four adenosine receptors (A1, A2a, A2b and A3). These receptors are G-Protein Coupled Receptors and have been proposed to stimulate adenylyl cyclase and increase intracellular cAMP. Although studies have show

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Olanrewaju, Hammed A., W. Qin, I. Feoktistov, Jean-Luc Scemama, and S. Jamal Mustafa. "Adenosine A2A and A2B receptors in cultured human and porcine coronary artery endothelial cells." American Journal of Physiology-Heart and Circulatory Physiology 279, no. 2 (2000): H650—H656. http://dx.doi.org/10.1152/ajpheart.2000.279.2.h650.

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We investigated the role of the cAMP link to the signal transduction mechanism coupled with adenosine A2A and A2Breceptors in cultured human coronary artery endothelial cells (HCAEC) and porcine coronary artery endothelial cells (PCAEC). 2-[4-[2-{2-[(4-aminophenyl)methylcarbonylamino]ethylaminocarbonyl}ethyl]phenyl]ethylamino-5′- ethylcarboxamidoadenosine (125I-PAPA-APEC) (PAPA-APEC) was used to demonstrate the specific binding in PCAEC membranes. The specific binding was saturable and reversible with a maximal number of binding sites (Bmax) of 240 fmol/mg protein, and scatchard analysis revea

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Awad, Alaa S., Liping Huang, Hong Ye, et al. "Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy." American Journal of Physiology-Renal Physiology 290, no. 4 (2006): F828—F837. http://dx.doi.org/10.1152/ajprenal.00310.2005.

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We previously demonstrated the anti-inflammatory effects and renal tissue protection in response to adenosine A2A-receptor (A2AR) activation in acute renal injury. We sought to extend these studies and determine the efficacy of A2AR agonists in a chronic model of renal injury. We hypothesized that A2A agonists mediate renal tissue protection in diabetic nephropathy by reducing glomerular inflammation. Diabetes was induced with single intravenous injection of streptozotocin in Sprague-Dawley rats (50 mg/kg). Increases in urinary albumin excretion (UAE) and plasma creatinine at week 6 in the dia

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Zhan, Enbo, Victoria J. McIntosh, and Robert D. Lasley. "Adenosine A2A and A2B receptors are both required for adenosine A1 receptor-mediated cardioprotection." American Journal of Physiology-Heart and Circulatory Physiology 301, no. 3 (2011): H1183—H1189. http://dx.doi.org/10.1152/ajpheart.00264.2011.

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All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A2A and/or A2B receptors modulate adenosine A1 receptor-mediated cardioprotection. Isolated perfused hearts of wild-type (WT), A2A knockout (KO), and A2BKO mice, perfused at constant pressure and constant heart rate, underwent 30 min of

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Lu, Qing, Elizabeth O. Harrington, Julie Newton, et al. "Adenosine protected against pulmonary edema through transporter- and receptor A2-mediated endothelial barrier enhancement." American Journal of Physiology-Lung Cellular and Molecular Physiology 298, no. 6 (2010): L755—L767. http://dx.doi.org/10.1152/ajplung.00330.2009.

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We have previously demonstrated that adenosine plus homocysteine enhanced endothelial basal barrier function and protected against agonist-induced barrier dysfunction in vitro through attenuation of RhoA activation by inhibition of isoprenylcysteine-O-carboxyl methyltransferase. In the current study, we tested the effect of elevated adenosine on pulmonary endothelial barrier function in vitro and in vivo. We noted that adenosine alone dose dependently enhanced endothelial barrier function. While adenosine receptor A1 or A3 antagonists were ineffective, an adenosine transporter inhibitor, NBTI,

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Baraldi, P. G., B. Cacciar, G. Spalluto, et al. "Current Developments of A2a Adenosine Receptor Antagonists." Current Medicinal Chemistry 2, no. 3 (1995): 707–22. http://dx.doi.org/10.2174/092986730203220223144628.

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<P>Adenosine regulates a wide range of physiological functions through specific cell membrane receptors. On the basis of pharmacological studies and molecular cloning, four distinct adenosine receptors have been identified and classified as A1, A2a. A2b and A3. These adenosine receptors are members of the G-protein-coupled receptor family. <P> An intense medicinal chemistry effort made over the last 20 years has led to a variety of selective adenosine receptor agonists and antagonists. While all the agonists thus far identified are related to the adenosine structure, the antagonist

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Hassanian, Seyed Mahdi, and Alireza R. Rezaie. "Adenosine Inhibits Pro-Inflammatory Thrombin Signaling In Endothelial Cells." Blood 122, no. 21 (2013): 1064. http://dx.doi.org/10.1182/blood.v122.21.1064.1064.

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Abstract Adenosine is an important regulatory metabolite which attenuates inflammation when it binds and activates the adenosine A2A receptor subtype on immune cells. However, the effect of adenosine on inflammatory responses in endothelial cells is mostly unknown. Thrombin as a known pro-inflammatory protease is involved in a variety of pathophysiological processes associated with inflammation in stimulated endothelial cells. The present study investigated the effect of adenosine on thrombin-mediated modulation of pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs).

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Feng, Ming-Guo, and L. Gabriel Navar. "Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A2B receptor activation." American Journal of Physiology-Renal Physiology 299, no. 2 (2010): F310—F315. http://dx.doi.org/10.1152/ajprenal.00149.2010.

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Adenosine is an important paracrine agent regulating renal vascular tone via adenosine A1 and A2 receptors. While A2B receptor message and protein have been localized to preglomerular vessels, functional evidence on the role of A2B receptors in mediating the vasodilator action of adenosine on afferent arterioles is not available. The present study determined the role of A2B receptors in mediating the afferent arteriolar dilation and compared the effects of A2B and A2A receptor blockade on afferent arterioles. We used the rat in vitro blood-perfused juxtamedullary nephron technique combined wit

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Borgland, Stephanie L., Maria Castañón, Walter Spevak, and Fiona E. Parkinson. "Effects of propentofylline on adenosine receptor activity in Chinese hamster ovary cell lines transfected with human A1, A2A, or A2B receptors and a luciferase reporter gene." Canadian Journal of Physiology and Pharmacology 76, no. 12 (1998): 1132–38. http://dx.doi.org/10.1139/y98-143.

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Propentofylline is neuroprotective in vivo, but its mechanism of action is not completely understood. Previously, propentofylline was shown to block adenosine transport processes, to inhibit three adenosine receptor subtypes, and to inhibit cAMP phosphodiesterase. We tested the effect of propentofylline on adenosine receptor function in Chinese hamster ovary (CHO) cells transfected with human adenosine A1, A2A, or A2B receptors and a luciferase reporter gene under control of a promoter sequence containing several copies of the cAMP response element. We investigated the concentration-dependent

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Kreisberg, M. S., E. P. Silldorff, and T. L. Pallone. "Localization of adenosine-receptor subtype mRNA in rat outer medullary descending vasa recta by RT-PCR." American Journal of Physiology-Heart and Circulatory Physiology 272, no. 3 (1997): H1231—H1238. http://dx.doi.org/10.1152/ajpheart.1997.272.3.h1231.

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Adenosine has a multitude of functions in the kidney, including vasoregulation of the renal vasculature. The actions of adenosine are mediated by its binding to specific receptors. Four adenosine-receptor subtypes have been cloned and sequenced, the A1, A2a, A2b, and the A3. In this study, the expression of individual adenosine-receptor subtype RNAs in outer medullary descending vasa recta (OMDVR) was investigated. Total RNA isolated from the outer medulla and microdissected, permeabilized OMDVR were subjected to reverse transcription-polymerase chain reaction (RT-PCR) with primers specific fo

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Kobayashi, Shuichi, Laura Conforti, and David E. Millhorn. "Gene expression and function of adenosine A2A receptor in the rat carotid body." American Journal of Physiology-Lung Cellular and Molecular Physiology 279, no. 2 (2000): L273—L282. http://dx.doi.org/10.1152/ajplung.2000.279.2.l273.

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The present study was undertaken to determine whether rat carotid bodies express adenosine (Ado) A2A receptors and whether this receptor is involved in the cellular response to hypoxia. Our results demonstrate that rat carotid bodies express the A2A and A2B Ado receptor mRNAs but not the A1 or A3 receptor mRNAs as determined by reverse transcriptase-polymerase chain reaction. In situ hybridization confirmed the expression of the A2A receptor mRNA. Immunohistochemical studies further showed that the A2A receptor is expressed in the carotid body and that it is colocalized with tyrosine hydroxyla

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Allen-Gipson, Diane S., Michael R. Blackburn, Daniel J. Schneider, et al. "Adenosine activation of A2B receptor(s) is essential for stimulated epithelial ciliary motility and clearance." American Journal of Physiology-Lung Cellular and Molecular Physiology 301, no. 2 (2011): L171—L180. http://dx.doi.org/10.1152/ajplung.00203.2010.

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Mucociliary clearance, vital to lung clearance, is dependent on cilia beat frequency (CBF), coordination of cilia, and the maintenance of periciliary fluid. Adenosine, the metabolic breakdown product of ATP, is an important modulator of ciliary motility. However, the contributions of specific adenosine receptors to key airway ciliary motility processes are unclear. We hypothesized that adenosine modulates ciliary motility via activation of its cell surface receptors (A1, A2A, A2B, or A3). To test this hypothesis, mouse tracheal rings (MTRs) excised from wild-type and adenosine receptor knockou

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Apasov, Sergey, Jiang-Fan Chen, Patrick Smith, and Michail Sitkovsky. "A2A receptor dependent and A2A receptor independent effects of extracellular adenosine on murine thymocytes in conditions of adenosine deaminase deficiency." Blood 95, no. 12 (2000): 3859–67. http://dx.doi.org/10.1182/blood.v95.12.3859.

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Abstract Adenosine deaminase (ADA) deficiency causes severe combined immunodeficiency (SCID) and is accompanied by T-cell depletion and accumulation of both intracellular and extracellular adenosine (extAdo) and deoxyadenosine. To better understand the causes of T-cell depletion in vivo and to discriminate between extracellular and intracellular effects of exogenously added adenosine in vitro, we investigated mechanisms of 2 different effects of adenosine on murine thymocytes. These effects of adenosine include direct induction of apoptosis in about 6% to 15% thymocytes and inhibition of T-cel

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Apasov, Sergey, Jiang-Fan Chen, Patrick Smith, and Michail Sitkovsky. "A2A receptor dependent and A2A receptor independent effects of extracellular adenosine on murine thymocytes in conditions of adenosine deaminase deficiency." Blood 95, no. 12 (2000): 3859–67. http://dx.doi.org/10.1182/blood.v95.12.3859.012k48_3859_3867.

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Adenosine deaminase (ADA) deficiency causes severe combined immunodeficiency (SCID) and is accompanied by T-cell depletion and accumulation of both intracellular and extracellular adenosine (extAdo) and deoxyadenosine. To better understand the causes of T-cell depletion in vivo and to discriminate between extracellular and intracellular effects of exogenously added adenosine in vitro, we investigated mechanisms of 2 different effects of adenosine on murine thymocytes. These effects of adenosine include direct induction of apoptosis in about 6% to 15% thymocytes and inhibition of T-cell recepto

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Supramongkonset, Jatuporn, Sarun Duangsuwan, Myo Myint Maw, and Sathaporn Promwong. "Empirical Path Loss Channel Characterization Based on Air-to-Air Ground Reflection Channel Modeling for UAV-Enabled Wireless Communications." Wireless Communications and Mobile Computing 2021 (July 30, 2021): 1–10. http://dx.doi.org/10.1155/2021/5589487.

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The purpose of this work was to investigate the air-to-air channel model (A2A-CM) for unmanned aerial vehicle- (UAV-) enabled wireless communications. Specifically, a low-altitude small UAV needs to characterize the propagation mechanisms from ground reflection. In this paper, the empirical path loss channel characterizations of A2A ground reflection CM based on different scenarios were presented by comparing the wireless communication modules for UAVs. Two types of wireless communication modules both WiFi 2.4 GHz and LoRa 868 MHz frequency were deployed to study the path loss channel characte

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Rickles, Richard J., Laura Pierce, Thomas Giordano, et al. "Adenosine A2A Receptor Agonism and PDE Inhibition: A Synergistic Multi-Target Mechanism Discovered through Systematic Combination Screening in Multiple Myeloma." Blood 112, no. 11 (2008): 847. http://dx.doi.org/10.1182/blood.v112.11.847.847.

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Abstract Using a combination high throughput screening technology, we have discovered an unexpected synergistic interaction between adenosine A2A receptor (A2A) agonism and phosphodiesterase (PDE) inhibition that displays substantial activity in preclinical Multiple Myeloma (MM) models. High throughput combination screening allows the systematic testing of combinations of approved drugs and other biologically active molecules in cell based assays of tumor cell proliferation and viability. In this approach we generate a dose matrix for each chemical combination, capturing the combined activity

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De Filippo, Elisabetta, Sonja Hinz, Veronica Pellizzari, et al. "A2A and A2B adenosine receptors: The extracellular loop 2 determines high (A2A) or low affinity (A2B) for adenosine." Biochemical Pharmacology 172 (February 2020): 113718. http://dx.doi.org/10.1016/j.bcp.2019.113718.

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Shi, Yanrong, Xiaoguang Liu, Debebe Gebremedhin, John R. Falck, David R. Harder, and Raymond C. Koehler. "Interaction of Mechanisms Involving Epoxyeicosatrienoic Acids, Adenosine Receptors, and Metabotropic Glutamate Receptors in Neurovascular Coupling in Rat Whisker Barrel Cortex." Journal of Cerebral Blood Flow & Metabolism 28, no. 1 (2007): 111–25. http://dx.doi.org/10.1038/sj.jcbfm.9600511.

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Adenosine, astrocyte metabotropic glutamate receptors (mGluRs), and epoxyeicosatrienoic acids (EETs) have been implicated in neurovascular coupling. Although A2A and A2B receptors mediate cerebral vasodilation to adenosine, the role of each receptor in the cerebral blood flow (CBF) response to neural activation remains to be fully elucidated. In addition, adenosine can amplify astrocyte calcium, which may increase arachidonic acid metabolites such as EETs. The interaction of these pathways was investigated by determining if combined treatment with antagonists exerted an additive inhibitory eff

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Jackson, Edwin K., Chongxue Zhu, and Stevan P. Tofovic. "Expression of adenosine receptors in the preglomerular microcirculation." American Journal of Physiology-Renal Physiology 283, no. 1 (2002): F41—F51. http://dx.doi.org/10.1152/ajprenal.00232.2001.

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The purpose of this study was to systematically investigate the abundance of each of the adenosine receptor subtypes in the preglomerular microcirculation vs. other vascular segments and vs. the renal cortex and medulla. Rat preglomerular microvessels (PGMVs) were isolated by iron oxide loading followed by magnetic separation. For comparison, mesenteric microvessels, segments of the aorta (thoracic, middle abdominal, and lower abdominal), renal cortex, and renal medulla were obtained by dissection. Adenosine receptor protein and mRNA expression were examined by Western blotting, Northern blott

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Ruiz-García, Almudena, Eva Monsalve, Laura Novellasdemunt, et al. "Cooperation of Adenosine with Macrophage Toll-4 Receptor Agonists Leads to Increased Glycolytic Flux through the Enhanced Expression of PFKFB3 Gene." Journal of Biological Chemistry 286, no. 22 (2011): 19247–58. http://dx.doi.org/10.1074/jbc.m110.190298.

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Macrophages activated through Toll receptor triggering increase the expression of the A2A and A2B adenosine receptors. In this study, we show that adenosine receptor activation enhances LPS-induced pfkfb3 expression, resulting in an increase of the key glycolytic allosteric regulator fructose 2,6-bisphosphate and the glycolytic flux. Using shRNA and differential expression of A2A and A2B receptors, we demonstrate that the A2A receptor mediates, in part, the induction of pfkfb3 by LPS, whereas the A2B receptor, with lower adenosine affinity, cooperates when high adenosine levels are present. pf

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Gaudry, Marine, Donato Vairo, Marion Marlinge, et al. "Adenosine and Its Receptors: An Expected Tool for the Diagnosis and Treatment of Coronary Artery and Ischemic Heart Diseases." International Journal of Molecular Sciences 21, no. 15 (2020): 5321. http://dx.doi.org/10.3390/ijms21155321.

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Adenosine is an endogenous nucleoside which strongly impacts the cardiovascular system. Adenosine is released mostly by endothelial cells and myocytes during ischemia or hypoxia and greatly regulates the cardiovascular system via four specific G-protein-coupled receptors named A1R, A2AR, A2BR, and A3R. Among them, A2 subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A2A receptor modulators are an opportunity for intense research by the pharmaceutical industry to develop new cardiovascular t

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Lasley, Robert D., Gentian Kristo, Byron J. Keith, and Robert M. Mentzer. "The A2a/A2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium." American Journal of Physiology-Heart and Circulatory Physiology 292, no. 1 (2007): H426—H431. http://dx.doi.org/10.1152/ajpheart.00675.2006.

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There is increasing evidence for interactions among adenosine receptor subtypes in the brain and heart. The purpose of this study was to determine whether the adenosine A2a receptor modulates the infarct size-reducing effect of preischemic administration of adenosine receptor agonists in intact rat myocardium. Adult male rats were submitted to in vivo regional myocardial ischemia (25 min) and 2 h reperfusion. Vehicle-treated rats were compared with rats pretreated with the A1 agonist 2-chloro- N6-cyclopentyladenosine (CCPA, 10 μg/kg), the nonselective agonist 5′- N-ethylcarboxamidoadenosine (N

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Wang, Jianjie, and Virginia H. Huxley. "Adenosine A2A receptor modulation of juvenile female rat skeletal muscle microvessel permeability." American Journal of Physiology-Heart and Circulatory Physiology 291, no. 6 (2006): H3094—H3105. http://dx.doi.org/10.1152/ajpheart.00526.2006.

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Little is known of the regulation of skeletal muscle microvascular exchange under resting or stimulating conditions. Adenosine (ADO) levels in skeletal muscle increase during physiological (exercise) and pathological (hypoxia, inflammation, and ischemia) conditions. Later stages of these pathologies are characterized by the loss of vascular barrier integrity. This study focused on determining which ADO receptor mediates the robust reduction in microvessel permeability to rat serum albumin ( PsRSA) observed in juvenile female rats. In microvessels isolated from abdominal skeletal muscle, ADO su

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Zhou, Xueping, Bunyen Teng, Stephen Tilley, and S. Jamal Mustafa. "A1 adenosine receptor negatively modulates coronary reactive hyperemia via counteracting A2A-mediated H2O2 production and KATP opening in isolated mouse hearts." American Journal of Physiology-Heart and Circulatory Physiology 305, no. 11 (2013): H1668—H1679. http://dx.doi.org/10.1152/ajpheart.00495.2013.

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We previously demonstrated that A2A, but not A2B, adenosine receptors (ARs) mediate coronary reactive hyperemia (RH), possibly by producing H2O2 and, subsequently, opening ATP-dependent K+ (KATP) channels in coronary smooth muscle cells. In this study, A1 AR knockout (KO), A3 AR KO, and A1 and A3 AR double-KO (A1/A3 DKO) mice were used to investigate the roles and mechanisms of A1 and A3 ARs in modulation of coronary RH. Coronary flow of isolated hearts was measured using the Langendorff system. A1 KO and A1/A3 DKO, but not A3 KO, mice showed a higher flow debt repayment [∼30% more than wild-t

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Kieć-Kononowicz, K., A. Drabczyńska, E. Pękala, et al. "New developments in A1 and A2 adenosine receptor antagonists." Pure and Applied Chemistry 73, no. 9 (2001): 1411–20. http://dx.doi.org/10.1351/pac200173091411.

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The aim of this article is to briefly present progress in the development of the potent adenosine receptor (AR) antagonists with high selectivity for either A1, A2A, or A2B ARs. The structural requirements for each AR subtype were discussed as well as their potential therapeutic use. In the search for new AR antagonists, series of imidazo-, pyrimido-, and diazepino-purindione derivatives as well as oxazolo-, oxazino-, and oxazepino-purindiones were designed, synthesized, and preliminarily evaluated in pharmacological studies. Oxygen-containing tricyclic derivatives were shown to be moderately

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Mahmood, T., U. Ekuere, F. Yeh, A. G. Good, and G. R. Stringam. "Molecular mapping of seed aliphatic glucosinolates in Brassica juncea." Genome 46, no. 5 (2003): 753–60. http://dx.doi.org/10.1139/g03-051.

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An RFLP genomic map with 316 loci was used to study the inheritance of aliphatic glucosinolates in Brassica juncea using doubled-haploid (DH) populations developed from a cross between RLM-514, an agronomically superior non-canola quality B. juncea (high erucic acid and high glucosinolates), and an agronomically poor canola quality B. juncea breeding line. Two QTLs (GSL-A2a and GSL-A2b) associated with 3-butenyl were consistent across years and locations, and explained 75% of the phenotypic variance in the population. Three QTLs (GSL-A2a, GSL-F, GSL-B3) affected 2-propenyl and explained 78% of

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Ngai, Al C., Ellicia F. Coyne, Joseph R. Meno, G. Alexander West, and H. Richard Winn. "Receptor subtypes mediating adenosine-induced dilation of cerebral arterioles." American Journal of Physiology-Heart and Circulatory Physiology 280, no. 5 (2001): H2329—H2335. http://dx.doi.org/10.1152/ajpheart.2001.280.5.h2329.

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The purpose of this study was to investigate the receptor subtypes that mediate the dilation of rat intracerebral arterioles elicited by adenosine. Penetrating arterioles were isolated from the rat brain, cannulated with the use of a micropipette system, and luminally pressurized to 60 mmHg. Both adenosine and the A2A receptor-selective agonist CGS-21680 induced dose-dependent vasodilation (−logEC50: 6.5 ± 0.2 and 8.6 ± 0.3, respectively). However, adenosine, which is capable of activating both A2A and A2B receptors, caused a greater maximal dilation than CGS-21680. The A2Areceptor-selective a

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Yang, Jiang-Ning, Olga Björklund, Karin Lindström-Törnqvist, et al. "Mice heterozygous for both A1 and A2A adenosine receptor genes show similarities to mice given long-term caffeine." Journal of Applied Physiology 106, no. 2 (2009): 631–39. http://dx.doi.org/10.1152/japplphysiol.90971.2008.

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Caffeine is believed to exert its stimulant effects by blocking A2A and A1 adenosine receptors (A2AR and A1R). Although a genetic knockout of A2AR eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number of A1Rs and A2ARs, achieved by deleting one of the two copies of the A1R and A2AR genes, would mimic some aspects of long-term caffeine ingestion. The A1R and A2AR double heterozygous (A1R-A2AR dHz) mice indeed had approximately one-half the number of A1R and

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Shringi, M., and C. Baregama. "1,3,7,8-SUBSTITUTED XANTHINE DERIVATIVES AS POTENTIAL ANTIASTHMATIC AGENTS WHICH ACT ON ADENOSINE RECEPTOR." INDIAN DRUGS 56, no. 07 (2019): 84–87. http://dx.doi.org/10.53879/id.56.07.11436.

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Asthma is one of the most common chronic diseases in modern society. There is a high prevalence of usage of complementary medicine for asthma. Xanthine derivatives which act on adenosine receptor have been cited as a most popular complementary treatment. This studys was undertaken to determine if there is any evidence for the clinical efficacy of xanthine derivatives for the treatment of asthma symptoms. This review highlights the more recent developments in the design and optimization of xanthine derivatives which act on A2A and A2B adenosine receptor. 1,3,8 and 1,3,7,8-substituted xanthine d

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Navarro, Gemma, Paulina Carriba, Jorge Gandí, et al. "Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D2, and Adenosine A2AG-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer." Scientific World JOURNAL 8 (2008): 1088–97. http://dx.doi.org/10.1100/tsw.2008.136.

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Functional interactions in signaling occur between dopamine D2(D2R) and cannabinoid CB1(CB1R) receptors, between CB1R and adenosine A2A(A2AR) receptors, and between D2R and A2AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A2AR-D2R, and CB1R-A2AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A2AR hetero-oligomers in living cells.

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Rickles, Richard J., Laura Pierce, Thomas Giordano, et al. "Adenosine A2A and Beta-2 Adrenergic Receptor Agonism: Novel Selective and Synergistic Multiple Myeloma Targets Discovered through Systematic Combination Screening." Blood 112, no. 11 (2008): 384. http://dx.doi.org/10.1182/blood.v112.11.384.384.

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Abstract Using a high throughput combination screening strategy, we have discovered that agonism of either adenosine A2A receptors (A2A) or beta-2 adrenergic receptors (bAR) demonstrate significant, synergistic, anti-proliferative effects in preclinical Multiple Myeloma (MM) models. Using quantitative synergy analysis, we observe that A2A and bAR agonists have significant anti-proliferative effects in a broad panel of 10 MM cell lines when combined with each other or with standard MM agents. Individual A2A agonists CGS-21680 and HE-NECA inhibited proliferation 25–80% with EC50s ranging from 2–

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Casanovas, Mireia, Irene Reyes-Resina, Alejandro Lillo, et al. "Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors." International Journal of Molecular Sciences 22, no. 5 (2021): 2743. http://dx.doi.org/10.3390/ijms22052743.

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Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A2A receptor (A2AR). First, we noticed that methamphetamine does not affect A2A functionality if the receptor is expressed in a heterologous system. However, A2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB1 receptor (CB1R) and the sigma 1 receptor

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Herman-de-Sousa, Carina, Ana Rita Pinheiro, Diogo Paramos-de-Carvalho, et al. "Opposing Effects of Adenosine and Inosine in Human Subcutaneous Fibroblasts May Be Regulated by Third Party ADA Cell Providers." Cells 9, no. 3 (2020): 651. http://dx.doi.org/10.3390/cells9030651.

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Human subcutaneous fibroblasts (HSCF) challenged with inflammatory mediators release huge amounts of ATP, which rapidly generates adenosine. Given the nucleoside’s putative relevance in wound healing, dermal fibrosis, and myofascial pain, we investigated the role of its precursor, AMP, and of its metabolite, inosine, in HSCF cells growth and collagen production. AMP (30 µM) was rapidly (t½ 3 ± 1 min) dephosphorylated into adenosine by CD73/ecto-5′-nucleotidase. Adenosine accumulation (t½ 158 ± 17 min) in the extracellular fluid reflected very low cellular adenosine deaminase (ADA) activity. HS

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Garcia-Garcia, Lucia, Laia Olle, Margarita Martin, Jordi Roca-Ferrer, and Rosa Muñoz-Cano. "Adenosine Signaling in Mast Cells and Allergic Diseases." International Journal of Molecular Sciences 22, no. 10 (2021): 5203. http://dx.doi.org/10.3390/ijms22105203.

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Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-in

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Holyoak, Rhys, Ruan Vlok, Thomas Melhuish, et al. "Intra-articular Alpha-2 Agonists as an Adjunct to Local Anesthetic in Knee Arthroscopy: A Systematic Review and Meta-Analysis." Journal of Knee Surgery 32, no. 02 (2018): 138–45. http://dx.doi.org/10.1055/s-0038-1636909.

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AbstractThe infiltration of local anesthetic has been shown to reduce postoperative pain in knee arthroscopy. Several studies have shown that the addition of agents such as magnesium and nonsteroidal antiinflammatory drugs (NSAIDs) result in an increased time to first analgesia and overall reduction in pain. The aim of this systematic review and meta-analysis was to determine whether the addition of an α-2 agonist (A2A) to intra-articular local anesthetic, results in a reduction in postoperative pain. Four major databases were systematically searched for relevant randomized controlled trials (

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Borroto-Escuela, Dasiel O., Luca Ferraro, Manuel Narvaez, et al. "Multiple Adenosine-Dopamine (A2A-D2 Like) Heteroreceptor Complexes in the Brain and Their Role in Schizophrenia." Cells 9, no. 5 (2020): 1077. http://dx.doi.org/10.3390/cells9051077.

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In the 1980s and 1990s, the concept was introduced that molecular integration in the Central Nervous System could develop through allosteric receptor–receptor interactions in heteroreceptor complexes presents in neurons. A number of adenosine–dopamine heteroreceptor complexes were identified that lead to the A2A-D2 heteromer hypothesis of schizophrenia. The hypothesis is based on strong antagonistic A2A-D2 receptor–receptor interactions and their presence in the ventral striato-pallidal GABA anti-reward neurons leading to reduction of positive symptoms. Other types of adenosine A2A heterorecep

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Fan, Ming, Weixi Qin, and S. Jamal Mustafa. "Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model." American Journal of Physiology-Lung Cellular and Molecular Physiology 284, no. 6 (2003): L1012—L1019. http://dx.doi.org/10.1152/ajplung.00353.2002.

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We recently reported that adenosine caused bronchoconstriction and enhanced airway inflammation in an allergic mouse model. In this study, we further report the characterization of the subtype of adenosine receptor(s) involved in bronchoconstriction. 5′-( N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine agonist, elicited bronchoconstriction in a dose-dependent manner. Little effects of N 6-cyclopentyladenosine (A1-selective agonist) and 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine (A2A-selective agonist) compared with NECA were observed in this model. 2-Chlo

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He, Wenjie, Jeesun Park, Amitabha Mazumder, and Bruce Cronstein. "Adenosine Regulates Bone Metabolism Via A1, A2A and A2B Receptors in Bone Marrow Cells From Normal and Patients with Multiple Myeloma." Blood 120, no. 21 (2012): 4977. http://dx.doi.org/10.1182/blood.v120.21.4977.4977.

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Abstract Abstract 4977 Background: Multiple myeloma is characterized by osteolytic bone lesions, wherein coupled bone remodeling is disrupted with increased osteoclast activation and decreased osteoblast differentiation. We have previously demonstrated that adenosine, acting via A2A receptors, diminishes human and murine osteoclast formation and others have reported that adenosine, acting at A2Breceptors, promotes osteoblast differentiation in murine osteoblast precursors and cell lines. In this study, we examined the effect of adenosine on osteoblast and osteoclast differentiation derived fro

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