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Adenosine A2B receptor

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https://www.readbyqxmd.com/read/28713274/stimulation-of-adenosine-a2b-receptor-inhibits-endothelin-1-induced-cardiac-fibroblast-proliferation-and-%C3%AE-smooth-muscle-actin-synthesis-through-the-camp-epac-pi3k-akt-signaling-pathway
#1
Sarawuth Phosri, Ajaree Arieyawong, Kwanchai Bunrukchai, Warisara Parichatikanond, Akiyuki Nishimura, Motohiro Nishida, Supachoke Mangmool
Background and Purpose: Cardiac fibrosis is characterized by an increase in fibroblast proliferation, overproduction of extracellular matrix proteins, and the formation of myofibroblast that express α-smooth muscle actin (α-SMA). Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac fibrosis. Overstimulation of endothelin receptors induced cell proliferation, collagen synthesis, and α-SMA expression in cardiac fibroblasts. Although adenosine was shown to have cardioprotective effects, the molecular mechanisms by which adenosine A2 receptor inhibit ET-1-induced fibroblast proliferation and α-SMA expression in cardiac fibroblasts are not clearly identified...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28693553/interaction-between-saliva-s-adenosine-and-tick-parasitism-effects-on-feeding-and-reproduction
#2
Elen Anatriello, Carlo José Freire Oliveira, Nathália Baptista Oliveira, Andressa Fisch, Cristiane Maria Milanezi, João Santana da Silva, Isabel Kinney Ferreira de Miranda-Santos, Beatriz Rossetti Ferreira
BACKGROUND: It has recently been demonstrated that saliva from Rhipicephalus sanguineus ticks contains adenosine (ADO) and prostaglandin E2 (PGE2), two non-protein molecules that have significant immunomodulatory properties. These molecules can inhibit cytokine production by dendritic cells (DCs), while also reducing the expression of CD40 in these cells. However, more studies are needed for a better understanding of their participation in the feeding of ticks in vivo. This work, therefore, evaluated the importance of ADO during tick infestations...
July 10, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28676923/biochemical-and-pharmacological-role-of-a1-adenosine-receptors-and-their-modulation-as-novel-therapeutic-strategy
#3
Katia Varani, Fabrizio Vincenzi, Stefania Merighi, Stefania Gessi, Pier Andrea Borea
Adenosine, the purine nucleoside, mediates its effects through activation of four G-protein coupled adenosine receptors (ARs) named as A1, A2A, A2B and A3. In particular, A1ARs are distributed through the body, primarily inhibitory in the regulation of adenylyl cyclase activity and able to reduce the cyclic AMP levels. Considerable advances have been made in the pharmacological and molecular characterization of A1ARs, which had been proposed as targets for the discovery and drug design of antagonists, agonists and allosteric enhancers...
July 5, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28630344/retraction-for-zimmerman-et-al-signaling-through-hepatocellular-a2b-adenosine-receptors-dampens-ischemia-and-reperfusion-injury-of-the-liver
#4
(no author information available yet)
No abstract text is available yet for this article.
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28604342/role-of-adenosine-receptors-in-the-adipocyte-macrophage-interaction-during-obesity
#5
Miguel Meriño, Lautaro Briones, Verónica Palma, Kurt Herlitz, Carlos Escudero
Lipoinflamation is the inflammation generated in the adipose tissue. It can contribute to the development of insulin resistance. The lipoinflammation-associated mechanisms are related to the function of adipocytes and macrophages present in the adipose tissue. In this regard, the level of nucleoside adenosine is increased in individuals with obesity. Causes or consequences of this increase are unknown. Although, adenosine activating its receptors (A1, A2A, A2B and A3) is able to differentially modulate the function of adipocytes and macrophages, in order to avoid the reduction of insulin sensitivity and generate an anti-inflammatory state in subject with obesity...
June 2017: Endocrinología, diabetes y nutrición
https://www.readbyqxmd.com/read/28548944/the-adenosine-a2b-receptor-promotes-tumor-progression-of-bladder-urothelial-carcinoma-by-enhancing-mapk-signaling-pathway
#6
Yihong Zhou, Xi Chu, Fei Deng, Liang Tong, Guoxiong Tong, Ye Yi, Jianye Liu, Jin Tang, Yuxin Tang, Yang Xia, Yingbo Dai
The adenosine A2b receptor (A2bR) was considered to play an oncogenic role in many human malignancies. However, the expression and molecular function of A2bR in bladder urothelial carcinoma (BUC) have not been well elucidated. Herein, we found that the expression of A2bR was higher than other adenosine receptors in BUC tissues and cells, and it was upregulated in BUC tissues compared with matched normal bladder tissues. Furthermore, high expression of A2bR was associated with poor prognosis of patients with BUC...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28542132/inhibition-of-sdf-1-receptors-cxcr4-and-cxcr7-attenuates-acute-pulmonary-inflammation-via-the-adenosine-a2b-receptor-on-blood-cells
#7
Franziska Magdalena Konrad, Nadine Meichssner, Annette Bury, Kristian-Christos Ngamsri, Jörg Reutershan
Acute pulmonary inflammation is characterized by migration of polymorphonuclear neutrophils into the different compartments of the lung. Recent studies showed evidence that the chemokine stromal cell-derived factor (SDF)-1 and its receptors CXCR4 and CXCR7 influence migration of immune cells and their activity was linked to adenosine concentrations. We investigated the particular role of CXCR4- and CXCR7-inhibition and the potential link to the adenosine A2B-receptor, which plays an important anti-inflammatory role in the lung...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28529484/targeting-adenosine-receptors-for-the-treatment-of-cardiac-fibrosis
#8
REVIEW
Elizabeth A Vecchio, Paul J White, Lauren T May
Adenosine is a ubiquitous molecule with key regulatory and cytoprotective mechanisms at times of metabolic imbalance in the body. Among a plethora of physiological actions, adenosine has an important role in attenuating ischaemia-reperfusion injury and modulating the ensuing fibrosis and tissue remodeling following myocardial damage. Adenosine exerts these actions through interaction with four adenosine G protein-coupled receptors expressed in the heart. The adenosine A2B receptor (A2BAR) is the most abundant adenosine receptor (AR) in cardiac fibroblasts and is largely responsible for the influence of adenosine on cardiac fibrosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28507174/elevated-adenosine-induces-placental-dna-hypomethylation-independent-of-a2b-receptor-signaling-in-preeclampsia
#9
Aji Huang, Hongyu Wu, Takayuki Iriyama, Yujin Zhang, Kaiqi Sun, Anren Song, Hong Liu, Zhangzhe Peng, Lili Tang, Minjung Lee, Yun Huang, Xin Ni, Rodney E Kellems, Yang Xia
Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation...
May 15, 2017: Hypertension
https://www.readbyqxmd.com/read/28483262/lungs-donated-after-circulatory-death-and-prolonged-warm-ischemia-are-transplanted-successfully-after-enhanced-ex%C3%A2-vivo-lung-perfusion-using-adenosine-a2b-receptor-antagonism
#10
Eric J Charles, J Hunter Mehaffey, Ashish K Sharma, Yunge Zhao, Mark H Stoler, James M Isbell, Christine L Lau, Curtis G Tribble, Victor E Laubach, Irving L Kron
OBJECTIVE: The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. METHODS: Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP...
April 12, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28481238/the-adenosinergic-system-as-a-therapeutic-target-in-the-vasculature-new-ligands-and-challenges
#11
REVIEW
Joana Beatriz Sousa, Carmen Diniz
Adenosine is an adenine base purine with actions as a modulator of neurotransmission, smooth muscle contraction, and immune response in several systems of the human body, including the cardiovascular system. In the vasculature, four P1-receptors or adenosine receptors-A₁, A2A, A2B and A₃-have been identified. Adenosine receptors are membrane G-protein receptors that trigger their actions through several signaling pathways and present differential affinity requirements. Adenosine is an endogenous ligand whose extracellular levels can reach concentrations high enough to activate the adenosine receptors...
May 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28417934/expression-of-adenosine-a2b-receptor-and-adenosine-deaminase-in-rabbit-gastric-mucosa-ecl-cells
#12
Rosa María Arin, Ana Isabel Vallejo, Yuri Rueda, Olatz Fresnedo, Begoña Ochoa
Adenosine is readily available to the glandular epithelium of the stomach. Formed continuously in intracellular and extracellular locations, it is notably produced from ATP released in enteric cotransmission. Adenosine analogs modulate chloride secretion in gastric glands and activate acid secretion in isolated parietal cells through A2B adenosine receptor (A2BR) binding. A functional link between surface A2BR and adenosine deaminase (ADA) was found in parietal cells, but whether this connection is a general feature of gastric mucosa cells is unknown...
April 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28415011/design-and-synthesis-of-novel-xanthine-derivatives-as-potent-and-selective-a2b-adenosine-receptor-antagonists-for-the-treatment-of-chronic-inflammatory-airway-diseases
#13
Sujay Basu, Dinesh A Barawkar, Vidya Ramdas, Meena Patel, Yogesh Waman, Anil Panmand, Santosh Kumar, Sachin Thorat, Minakshi Naykodi, Arnab Goswami, B Srinivasa Reddy, Vandna Prasad, Sandhya Chaturvedi, Azfar Quraishi, Suraj Menon, Shalini Paliwal, Abhay Kulkarni, Vikas Karande, Indraneel Ghosh, Syed Mustafa, Siddhartha De, Vaibhav Jain, Ena Ray Banerjee, Sreekanth R Rouduri, Venkata P Palle, Anita Chugh, Kasim A Mookhtiar
Adenosine induces bronchial hyperresponsiveness and inflammation in asthmatics through activation of A2B adenosine receptor (A2BAdoR). Selective antagonists have been shown to attenuate airway reactivity and improve inflammatory conditions in pre-clinical studies. Hence, the identification of novel, potent and selective A2BAdoR antagonist may be beneficial for the potential treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). Towards this effort, we explored several prop-2-ynylated C8-aryl or heteroaryl substitutions on xanthine chemotype and found that 1-prop-2-ynyl-1H-pyrazol-4-yl moiety was better tolerated at the C8 position...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28368607/enantiospecific-recognition-at-the-a2b-adenosine-receptor-by-alkyl-2-cyanoimino-4-substituted-6-methyl-1-2-3-4-tetrahydropyrimidine-5-carboxylates
#14
Carlos Carbajales, Jhonny Azuaje, Ana Oliveira, María I Loza, José Brea, María I Cadavid, Christian F Masaguer, Xerardo García-Mera, Hugo Gutiérrez-de-Terán, Eddy Sotelo
A novel family of structurally simple, potent, and selective nonxanthine A2BAR ligands was identified, and its antagonistic behavior confirmed through functional experiments. The reported alkyl 2-cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahy-dropyrimidine-5-carboxylates (16) were designed by bioisosteric replacement of the carbonyl group at position 2 in a series of 3,4-dihydropyrimidin-2-ones. The scaffold (16) documented herein contains a chiral center at the heterocycle. Accordingly, the most attractive ligand of the series [(±)16b, Ki = 24...
April 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28344125/capadenoson-a-clinically-trialed-partial-adenosine-a1-receptor-agonist-can-stimulate-adenosine-a2b-receptor-biased-agonism
#15
Jo-Anne Baltos, Elizabeth A Vecchio, Matthew A Harris, Cheng Xue Qin, Rebecca H Ritchie, Arthur Christopoulos, Paul J White, Lauren T May
The adenosine A2B receptor (A2BAR) has been identified as an important therapeutic target in cardiovascular disease, however in vitro and in vivo targeting has been limited by the paucity of pharmacological tools, particularly potent agonists. Interestingly, 2-((6-amino-3,5-dicyano-4-(4-(cyclopropylmethoxy)phenyl)-2-pyridinyl)thio)acetamide (BAY60-6583), a potent and subtype-selective A2BAR agonist, has the same core structure as 2-amino-6-[[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methylsulfanyl]-4-[4-(2-hydroxyethoxy)phenyl]pyridine-3,5-dicarbonitril (capadenoson)...
July 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28317879/a-novel-method-for-screening-adenosine-receptor-specific-agonists-for-use-in-adenosine-drug-development
#16
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/28294142/inosine-attenuates-spontaneous-activity-in-the-rat-neurogenic-bladder-through-an-a2b-pathway
#17
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/28287473/structural-probing-and-molecular-modeling-of-the-a%C3%A2-adenosine-receptor-a-focus-on-agonist-binding
#18
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
#19
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...
February 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28252203/pathological-overproduction-the-bad-side-of-adenosine
#20
REVIEW
Pier Andrea Borea, Stefania Gessi, Stefania Merighi, Fabrizio Vincenzi, Katia Varani
Adenosine is an endogenous ubiquitous purine nucleoside, which is increased by hypoxia, ischaemia and tissue damage and mediates a number of physiopathological effects by interacting with four GPCRs, identified as A1 , A2A , A2B and A3 . Physiological and acutely increased adenosine is mostly associated with beneficial effects that include vasodilatation and a decrease in 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
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