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Adenosine A2B receptor

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https://www.readbyqxmd.com/read/28093236/extracellular-atp-and-adenosine-the-yin-and-yang-in-immune-responses
#1
REVIEW
M M Faas, T Sáez, P de Vos
Extracellular adenosine 5'-triphosphate (ATP) and adenosine molecules are intimately involved in immune responses. ATP is mostly a pro-inflammatory molecule and is released during hypoxic condition and by necrotic cells, as well as by activated immune cells and endothelial cells. However, under certain conditions, for instance at low concentrations or at prolonged exposure, ATP may also have anti-inflammatory properties. Extracellular ATP can activate both P2X and P2Y purinergic receptors. Extracellular ATP can be hydrolyzed into adenosine in a two-step enzymatic process involving the ectonucleotidases CD39 (ecto-apyrase) and CD73...
January 13, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28089906/adenosine-signaling-in-diabetes-mellitus-and-associated-cardiovascular-and-renal-complications
#2
REVIEW
Maria Peleli, Mattias Carlstrom
Diabetes mellitus is characterized by abnormal glucose and lipid metabolism, and subsequent hyperglycemia and dyslipidemia, which results from defects in pancreatic beta islets insulin secretion and/or decreased insulin sensitivity in metabolically active organs (i.e. liver, skeletal muscle and adipose tissue). Accumulating evidence highlights a critical role for the adenosine system in the regulation of insulin and glucose homeostasis and the pathophysiology of type 2 diabetes (T2D). Adenosine is a key diverse extracellular signaling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors (i...
January 12, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28075020/adenosine-receptors-regulate-gap-junction-coupling-of-the-human-cerebral-microvascular-endothelial-cells-hcmec-d3-by-ca-2-influx-through-cng-channels
#3
Almke Bader, Willem Bintig, Daniela Begandt, Anne Klett, Ina G Siller, Carola Gregor, Frank Schaarschmidt, Babette Weksler, Ignacio Romero, Pierre-Olivier Couraud, Stefan W Hell, Anaclet Ngezahayo
The human cerebral microvascular endothelial cell line hCMEC/D3 was used to characterize the physiological link between adenosine receptors and the gap junction coupling in endothelial cells of the blood-brain barrier. Expressed adenosine receptor subtypes and connexin (Cx) isoforms were identified by RT-PCR. Scrape loading/dye transfer was used to evaluate the impact of the A2A and A2B adenosine receptor subtype agonist 2-phenylaminoadenosine (2-PAA) on the gap junction coupling. We found that 2-PAA stimulated cAMP synthesis and enhanced gap junction coupling in a concentration-dependent manner...
January 11, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28010756/deregulation-of-adenosine-receptors-in-psoriatic-epidermis-an-option-for-therapeutic-treatment
#4
Stefania Merighi, Pier Andrea Borea, Katia Varani, Stefania Gessi
Purinergic signaling is involved in psoriasis, a chronic skin disease characterized by increased epidermis cell growth. In particular, Andrés et al. focus on the keratinocyte biology modulated by adenosine receptors providing evidence that the A2B subtype plays a prominent role in the reduction of keratinocyte proliferation whereas A2A and A2B agonists have antiinflammatory effects independent of adenosine receptors. The authors report that psoriatic epidermis presents a deregulated adenosine receptor expression profile with reduced A2B and increased A2A...
January 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27974241/a2b-adenosine-receptors-stimulate-il-6-production-in-primary-murine-microglia-through-p38-mapk-kinase-pathway
#5
Stefania Merighi, Serena Bencivenni, Fabrizio Vincenzi, Katia Varani, Pier Andrea Borea, Stefania Gessi
The hallmark of neuroinflammation is the activation of microglia, the immunocompetent cells of the CNS, releasing a number of proinflammatory mediators implicated in the pathogenesis of neuronal diseases. Adenosine is an ubiquitous autacoid regulating several microglia functions through four receptor subtypes named A1, A2A, A2B and A3 (ARs), that represent good targets to suppress inflammation occurring in CNS. Here we investigated the potential role of ARs in the modulation of IL-6 secretion and cell proliferation in primary microglial cells...
December 11, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27965423/increased-activity-of-tnap-compensates-for-reduced-adenosine-production-and-promotes-ectopic-calcification-in-the-genetic-disease-acdc
#6
Hui Jin, Cynthia St Hilaire, Yuting Huang, Dan Yang, Natalia I Dmitrieva, Alejandra Negro, Robin Schwartzbeck, Yangtengyu Liu, Zhen Yu, Avram Walts, Jean-Michel Davaine, Duck-Yeon Lee, Danielle Donahue, Kevin S Hsu, Jessica Chen, Tao Cheng, William Gahl, Guibin Chen, Manfred Boehm
ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5'-ectonucleotidase that converts extracellular adenosine monophosphate to adenosine. ACDC patients display progressive calcification of lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), which converts pyrophosphate (PPi) to inorganic phosphate (Pi), and extracellular purine metabolism play important roles in other inherited forms of vascular calcification...
December 13, 2016: Science Signaling
https://www.readbyqxmd.com/read/27919679/regulation-of-protein-kinase-c-epsilon-and-its-age-dependence
#7
Chen Kang, Jingping Qin, Wil Osei, Keli Hu
Protein kinase C (PKC) is an important mediator in the cardioprotection of ischemic preconditioning and has been shown to translocate to mitochondria upon activation. However, little is known about the cellular signaling underlying the translocation of PKC isoforms to mitochondria and its age-dependence. The present study aimed to explore whether adenosine-induced translocation of PKCε to mitochondria is mediated by caveolin-3 and/or adenosine A2B receptor/PI3 kinase mediated signaling, and whether the mitochondrial targeting of PKCε is age-related...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27915051/low-but-not-high-dose-caffeine-is-a-readily-available-probe-for-adenosine-actions
#8
REVIEW
Bertil B Fredholm, Jiangning Yang, Yingqing Wang
Caffeine is very widely used and knowledge of its mode of action can be used to gain an understanding of basal physiological regulation. This review makes the point that caffeine is - in low doses - an antagonist of adenosine acting at A1, A2A and A2B receptors. We use published and unpublished data to make the point that high dose effects of caffeine are not only qualitatively different but have a different underlying mechanism. Therefore one must be careful in only using epidemiological or experimental data where rather low doses of caffeine are used to draw conclusions about the physiology and pathophysiology of adenosine...
November 30, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27911956/adenosine-stimulate-proliferation-and-migration-in-triple-negative-breast-cancer-cells
#9
Miriam Fernandez-Gallardo, Ricardo González-Ramírez, Alejandro Sandoval, Ricardo Felix, Eduardo Monjaraz
Emerging evidence suggests that the adenosine (Ado) receptors may play crucial roles in tumor progression. Here, we show that Ado increases proliferation and migration in a triple negative breast cancer model, the MDA-MB 231 cell line. The use of specific agonists and antagonists evidenced that these effects depend on the activation of the A2B receptor, which then triggers an intracellular response mediated by the adenylate cyclase/PKA/cAMP signaling pathway. Ado also increases the expression of NaV1.5 channels, a potential biomarker in breast cancer...
2016: PloS One
https://www.readbyqxmd.com/read/27889899/a1-adenosine-receptor-activation-modulates-central-nervous-system-development-and-repair
#10
REVIEW
Shirin Kashfi, Kamran Ghaedi, Hossein Baharvand, Mohammad Hossein Nasr-Esfahani, Mohammad Javan
Adenosine is an endogenous, autacoid purine nucleoside which performs many important biological roles, particularly during stressful events. Adenosine can signal through four adenosine receptor (AR) subtypes: A1, A2A, A2B, and A3. Of these, adenosine A1 receptor (A1AR) has a broad, wide distribution throughout different vertebrate cell types and the highest affinity to adenosine. The A1AR-dependent action of adenosine is well documented in reports from numerous studies that have used different selective A1AR agonists and antagonists as well as in animals that have a genetically manipulated A1AR gene...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27865066/newly-synthesized-camp-is-integrated-at-a-membrane-protein-complex-signalosome-to-ensure-receptor-response-specificity
#11
Raquel Guinzberg, Antonio Díaz-Cruz, Carlos Acosta-Trujillo, María Magdalena Vilchis-Landeros, Héctor Vázquez-Meza, Carlos Lozano-Flores, Natalia Chiquete-Felix, Alfredo Varela-Echavarría, Salvador Uribe-Carvajal, Héctor Riveros-Rosas, Enrique Piña
Spatiotemporal regulation of cAMP within the cell is required to achieve receptor-specific responses. The mechanism through which the cell selects a specific response to newly synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and independent cAMP-responsive signaling protein macrocomplexes that produce, use, degrade, and regulate their own nondiffusible (sequestered) cAMP pool to achieve their specific responses. Each complex responds to the stimulation of an adenosine G protein-coupled receptor (Ado-GPCR), bound to either A2A or A2B , but not simultaneously to both...
November 19, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27842891/a2b-adenosine-receptor-antagonists-design-synthesis-and-biological-evaluation-of-novel-xanthine-derivatives
#12
Sujay Basu, Dinesh A Barawkar, Vidya Ramdas, Yogesh Waman, Meena Patel, Anil Panmand, Santosh Kumar, Sachin Thorat, Rajesh Bonagiri, Dilip Jadhav, Partha Mukhopadhyay, Vandna Prasad, B Srinivasa Reddy, Arnab Goswami, Sandhya Chaturvedi, Suraj Menon, Azfar Quraishi, Indraneel Ghosh, Sushant Dusange, Shalini Paliwal, Abhay Kulkarni, Vikas Karande, Rhishikesh Thakre, Gaurav Bedse, Sreekanth Rouduri, Jayasagar Gundu, Venkata P Palle, Anita Chugh, Kasim A Mookhtiar
A2BAdoR is a low affinity adenosine receptor that functions by Gs mediated elevation of cAMP and subsequent downstream signaling. The receptor has been implicated in lung inflammatory disorders like COPD and asthma. Several potent and selective A2BAdoR antagonists have been reported in literature, however most of the compounds suffer from poor pharmacokinetic profile. Therefore, with the aim to identify novel, potent and selective A2BAdoR antagonists with improved pharmacokinetic properties, we first explored more constrained form of MRS-1754 (4)...
November 8, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27812030/predicting-subtype-selectivity-for-adenosine-receptor-ligands-with-three-dimensional-biologically-relevant-spectrum-brs-3d
#13
Song-Bing He, Ben Hu, Zheng-Kun Kuang, Dong Wang, De-Xin Kong
Adenosine receptors (ARs) are potential therapeutic targets for Parkinson's disease, diabetes, pain, stroke and cancers. Prediction of subtype selectivity is therefore important from both therapeutic and mechanistic perspectives. In this paper, we introduced a shape similarity profile as molecular descriptor, namely three-dimensional biologically relevant spectrum (BRS-3D), for AR selectivity prediction. Pairwise regression and discrimination models were built with the support vector machine methods. The average determination coefficient (r(2)) of the regression models was 0...
November 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27792010/theobromine-induced-changes-in-a1-purinergic-receptor-gene-expression-and-distribution-in-a-rat-brain-alzheimer-s-disease-model
#14
Jesus Mendiola-Precoma, Karla Padilla, Alfredo Rodríguez-Cruz, Laura C Berumen, Ricardo Miledi, Guadalupe García-Alcocer
Dementia caused by Alzheimer's disease (AD) is mainly characterized by accumulation in the brain of extra- and intraneuronal amyloid-β (Aβ) and tau proteins, respectively, which selectively affect specific regions, particularly the neocortex and the hippocampus. Sporadic AD is mainly caused by an increase in apolipoprotein E, a component of chylomicrons, which are cholesterol transporters in the brain. Recent studies have shown that high lipid levels, especially cholesterol, are linked to AD. Adenosine is an atypical neurotransmitter that regulates a wide range of physiological functions by activating four P1 receptors (A1, A2A, A2B, and A3) and P2 purinergic receptors that are G protein-coupled...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27770217/partial-adenosine-a1-agonist-in-heart-failure
#15
Wilfried Dinh, Barbara Albrecht-Küpper, Mihai Gheorghiade, Adriaan A Voors, Michael van der Laan, Hani N Sabbah
Adenosine exerts a variety of physiological effects by binding to cell surface G-protein-coupled receptor subtypes, namely, A1, A2a, A2b, and A3. The central physiological role of adenosine is to preclude tissue injury and promote repair in response to stress. In the heart, adenosine acts as a cytoprotective modulator, linking cardiac function to metabolic demand predominantly via activation of adenosine A1 receptors (A1Rs), which leads to inhibition of adenylate cyclase activity, modulation of protein kinase C, and opening of ATP-sensitive potassium channels...
October 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27757725/adenosine-a2a-and-a2b-receptor-substantially-attenuate-ischemia-reperfusion-injury-in-septic-rat-hearts
#16
Hendrik Busse, Diane Bitzinger, Klaus Höcherl, Timo Seyfried, Michael Gruber, Bernhard M Graf, York A Zausig
INTRODUCTION: Mechanical and morphological ischemia and reperfusion (I/R) injury is reduced in septic hearts. The mechanism behind this "cardioprotection" is less well understood. As adenosine receptors play a major role for cardioprotection in non-septic hearts, we investigated the influence of adenosine receptors in a model of I/R in septic hearts. METHODS: SHAM operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats (n = 60)...
December 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27729268/role-of-adenosine-a2b-receptor-overexpression-in-tumor-progression
#17
REVIEW
Cesar Sepúlveda, Iván Palomo, Eduardo Fuentes
The adenosine A2b receptor is a G-protein coupled receptor. Its activation occurs with high extracellular adenosine concentration, for example in inflammation or hypoxia. These conditions are generated in the tumor environment. Studies show that A2b receptor is overexpressed in various tumor lines and biopsies from patients with different cancers. This suggests that A2b receptor can be used by tumor cells to promote progression. Thus A2b participates in different events, such as angiogenesis and metastasis, besides exerting immunomodulatory effects that protect tumor cells...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27693637/the-a2b-adenosine-receptor-antagonist-psb-603-promotes-oxidative-phosphorylation-and-ros-production-in-colorectal-cancer-cells-via-adenosine-receptor-independent-mechanism
#18
Christina Mølck, James Ryall, Laura M Failla, Janine L Coates, Jean-Marc Pascussi, Joan K Heath, Gregory Stewart, Frédéric Hollande
PURPOSE: Adenosine is a multifaceted regulator of tumor progression. It modulates immune cell activity as well as acting directly on tumor cells. The A2b adenosine receptor (A2b-AR) is thought to be an important mediator of these effects. In this study we sought to analyze the contribution of the A2b-AR to the behavior of colorectal cancer cells. PRINCIPAL RESULTS: The A2b-AR antagonist PSB-603 changed cellular redox state without affecting cellular viability. Quantification of cellular bioenergetics demonstrated that PSB-603 increased basal oxygen consumption rates, indicative of enhanced mitochondrial oxidative phosphorylation...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27621729/cyclic-amp-represents-a-crucial-component-of-treg-cell-mediated-immune-regulation
#19
REVIEW
Matthias Klein, Tobias Bopp
T regulatory (Treg) cells are one of the key players in the immune tolerance network, and a plethora of manuscripts have described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate as to which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP), which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted, the source and the mechanism of action of cAMP are less clear, and a multitude of seemingly contradictory data allow for, in principle, two different scenarios of cAMP-mediated suppression...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27606311/adenosine-a2b-receptor-from-cell-biology-to-human-diseases
#20
REVIEW
Ying Sun, Pingbo Huang
Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR's functions, including certain seemingly paradoxical functions of the receptor...
2016: Frontiers in Chemistry
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