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Adenosine A2 Receptor

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https://www.readbyqxmd.com/read/28406726/role-of-heterotrimeric-g-proteins-in-platelet-activation-and-clot-formation-in-platelets-treated-with-integrin-%C3%AE-iib%C3%AE-3-inhibitor
#1
Ivan Budnik, Boris Shenkman, Hagit Hauschner, Isaac Zilinsky, Naphtali Savion
Mechanisms of platelet activation are triggered by thrombin, adenosine diphosphate (ADP), epinephrine, thromboxane A2, and other soluble agonists which induce signaling via heterotrimeric Gαq, Gαi, and Gα12/13 proteins. We have undertaken a study addressing the contribution of these G proteins to platelet activation and clot formation in the presence of eptifibatide, thus excluding outside-in signaling provided by integrin αIIbβ3-fibrinogen engagement. Selective and combined activation of the G proteins was achieved by using combinations of platelet agonists and inhibitors...
April 13, 2017: Platelets
https://www.readbyqxmd.com/read/28371382/inhibitory-effects-of-urothelium-related-factors
#2
Na N Guan, Lars E Gustafsson, Karl Svennersten
The urothelium of the bladder has long been recognized as a protective barrier between detrusor and urine. In recent years, it has become more evident that the urothelium plays a role as an active source of mediators. The urothelium can release neurotransmitters and modulators such as acetylcholine, ATP, nitric oxide, prostaglandins and neuropeptides. They exert both excitatory and inhibitory effects in modulating urinary tract motility. In addition, several studies have reported the existence of an urothelium-derived unknown inhibitory factor in the urinary bladder...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28356704/osmotic-regulation-of-nfat5-expression-in-rpe-cells-the-involvement-of-purinergic-receptor-signaling
#3
Margrit Hollborn, Sarah Fischer, Heidrun Kuhrt, Peter Wiedemann, Andreas Bringmann, Leon Kohen
PURPOSE: Systemic hypertension is a risk factor for age-related neovascular retinal diseases. The major condition that induces hypertension is the intake of dietary salt (NaCl) resulting in increased extracellular osmolarity. High extracellular NaCl was has been shown to induce angiogenic factor production in RPE cells, in part via the transcriptional activity of nuclear factor of activated T cell 5 (NFAT5). Here, we determined the signaling pathways that mediate the osmotic expression of the NFAT5 gene in RPE cells...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28344879/prostaglandin-e2-mediated-adenosinergic-effects-on-cd14-cells-self-amplifying-immunosuppression-in-cancer
#4
Saly Al-Taei, Josephine Salimu, Lisa K Spary, Aled Clayton, Jason F Lester, Zsuzsanna Tabi
CD39 and CD73 are surface-expressed ectonucleotidases that hydrolyze ATP in a highly regulated, serial manner into ADP, AMP and adenosine. The end product, adenosine, has both tumor-promoting and immunosuppressive effects. The aim of this study was to determine CD73 expression on immune cells in pleural effusion (PE) in order to have a better understanding of the immune environment in mesothelioma. PE- or blood-derived CD14(+) cells of mesothelioma patients and healthy donors were analyzed by flow cytometry for the expression of CD39 and CD73...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28224791/copper-catalyzed-tandem-o-arylation-oxidative-cross-coupling-synthesis-of-chromone-fused-pyrazoles
#5
Owk Obulesu, K Harish Babu, Jagadeesh Babu Nanubolu, Surisetti Suresh
Intermolecular tandem copper-catalyzed O-arylation-oxidative acylation (cross dehydrogenative coupling-CDC) has been developed under air as an oxidant. The reaction between 2,4-dihydro-3H-pyrazol-3-ones and ortho-halo aryl carboxaldehydes furnished the corresponding chromone fused pyrazoles, in a straightforward manner. The synthetic utility of the presented tandem catalysis has been demonstrated with the synthesis of an A2-subtype selective adenosine receptor antagonist in only two steps.
March 7, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28219781/adenosine-a2-receptor-activation-ameliorates-mitochondrial-oxidative-stress-upon-reperfusion-through-the-posttranslational-modification-of-ndufv2-subunit-of-complex-i-in-the-heart
#6
Jingman Xu, Xiyun Bian, Yuan Liu, Lan Hong, Tianming Teng, Yuemin Sun, Zhelong Xu
While it is well known that adenosine receptor activation protects the heart from ischemia/reperfusion injury, the precise mitochondrial mechanism responsible for the action remains unknown. This study probed the mitochondrial events associated with the cardioprotective effect of 5'-(N-ethylcarboxamido) adenosine (NECA), an adenosine A2 receptor agonist. Isolated rat hearts were subjected to 30min ischemia followed by 10min of reperfusion, whereas H9c2 cells experienced 20min ischemia and 10min reperfusion...
February 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28174424/targeting-a2-adenosine-receptors-in-cancer
#7
REVIEW
David Allard, Martin Turcotte, John Stagg
Tumor cells use various ways to evade anti-tumor immune responses. Adenosine, a potent immunosuppressive metabolite, is often found elevated in the extracellular tumor microenvironment. Therefore, targeting adenosine-generating enzymes (CD39 and CD73) or adenosine receptors has emerged as a novel means to stimulate anti-tumor immunity. In particular, the A2 (A2a and A2b) adenosine receptors exhibit similar immunosuppressive and pro-angiogenic functions, yet have distinct biological roles in cancer. In this review, we describe the common and distinct biological consequences of A2a and A2b adenosine receptor signaling in cancer...
April 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28120151/the-ying-and-yang-of-adenosine-a1-and-a2a-receptors-on-erk1-2-activation-in-a-rat-model-of-global-cerebral-ischemia-reperfusion-injury
#8
Reham M Atef, Azza M Agha, Abdel-Rahman A Abdel-Rhaman, Noha N Nassar
Adenosine impacts cerebral ischemia reperfusion (IR) through the inhibitory A1 and the excitatory A2 receptors. The present study aimed at investigating the contrasting role of pERK1/2 in mediating adenosine A1R (protective) versus A2AR (deleterious) effects in IR. Male Wistar rats subjected to bilateral carotid occlusion (45 min) followed by reperfusion (24 h) exhibited increased pERK1/2 activity, downstream from DAG pathway, along with increases in hippocampal glutamate, c-Fos, NF-κB, TNF-α, iNOS, TBARS, cytochrome c, caspase-3, BDNF, Nrf2, and IL-10 contents...
January 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27789556/protective-effects-of-ticagrelor-on-myocardial-injury-after-infarction
#9
Gemma Vilahur, Manuel Gutiérrez, Laura Casani, Lourdes Varela, Antoni Capdevila, Guillem Pons-Lladó, Francesc Carreras, Leif Carlsson, Alberto Hidalgo, Lina Badimon
BACKGROUND: The P2Y12 receptor antagonist ticagrelor has been shown to be clinically superior to clopidogrel. Although the underlying mechanisms remain elusive, ticagrelor may exert off-target effects through adenosine-related mechanisms. We aimed to investigate whether ticagrelor reduces myocardial injury to a greater extent than clopidogrel after myocardial infarction (MI) at a similar level of platelet inhibition and to determine the underlying mechanisms. METHODS: Pigs received the following before MI induction: (1) placebo-control; (2) a loading dose of clopidogrel (600 mg); (3) a loading dose of ticagrelor (180 mg); or (4) a loading dose of ticagrelor followed by an adenosine A1/A2-receptor antagonist [8-(p-sulfophenyl)theophylline, 4 mg/kg intravenous] to determine the potential contribution of adenosine in ticagrelor-related cardioprotection...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27753934/os-05-09-reduced-vasodilator-efficiency-of-adenosine-in-the-brainstem-of-young-spontaneously-hypertensive-rats
#10
Dmitry Mayorov, Sergey Kasparov, Julian Paton
OBJECTIVE: Functional defects in purinergic neurotransmission, and specifically adenosine A1 receptor, have been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). Here, we examined the role of adenosine receptors in regulating cerebrovascular function in pre-hypertensive SHR. DESIGN AND METHOD: Changes in the diameter of pial arterioles (20-100 μm) in response to adenosine A1 and A2 receptor agonists were assessed after pre-constriction with the thromboxane agonist U46619 in slices from the brainstem and cortex of 4-6 week-old Wistar and SHR...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643329/os-05-09-reduced-vasodilator-efficiency-of-adenosine-in-the-brainstem-of-young-spontaneously-hypertensive-rats
#11
Dmitry Mayorov, Sergey Kasparov, Julian Paton
OBJECTIVE: Functional defects in purinergic neurotransmission, and specifically adenosine A1 receptor, have been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). Here, we examined the role of adenosine receptors in regulating cerebrovascular function in pre-hypertensive SHR. DESIGN AND METHOD: Changes in the diameter of pial arterioles (20-100 μm) in response to adenosine A1 and A2 receptor agonists were assessed after pre-constriction with the thromboxane agonist U46619 in slices from the brainstem and cortex of 4-6 week-old Wistar and SHR...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27482267/influence-of-thromboxane-a2-on-the-regulation-of-adenosine-triphosphate-sensitive-potassium-channels-in-mouse-ventricular-myocytes
#12
In Seok Jeong, Hwa Jin Cho, Jeong Gwan Cho, Sang Hyung Kim, Kook Joo Na, Jong-Keun Kim
BACKGROUND AND OBJECTIVES: Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels play an important role in myocardial protection. We examined the effects of thromboxane A2 on the regulation of KATP channel activity in single ventricular myocytes. SUBJECTS AND METHODS: Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at -60 mV holding potential during the perfusion of an ATP-free K-5 solution...
July 2016: Korean Circulation Journal
https://www.readbyqxmd.com/read/27462812/structure-of-the-adenosine-a-2a-receptor-bound-to-an-engineered-g-protein
#13
Byron Carpenter, Rony Nehmé, Tony Warne, Andrew G W Leslie, Christopher G Tate
G-protein-coupled receptors (GPCRs) are essential components of the signalling network throughout the body. To understand the molecular mechanism of G-protein-mediated signalling, solved structures of receptors in inactive conformations and in the active conformation coupled to a G protein are necessary. Here we present the structure of the adenosine A(2A) receptor (A(2A)R) bound to an engineered G protein, mini-Gs, at 3.4 Å resolution. Mini-Gs binds to A(2A)R through an extensive interface (1,048 Å2) that is similar, but not identical, to the interface between Gs and the β2-adrenergic receptor...
August 4, 2016: Nature
https://www.readbyqxmd.com/read/27365148/how-does-adenosine-control-neuronal-dysfunction-and-neurodegeneration
#14
REVIEW
Rodrigo A Cunha
The adenosine modulation system mostly operates through inhibitory A1 (A1 R) and facilitatory A2A receptors (A2A R) in the brain. The activity-dependent release of adenosine acts as a brake of excitatory transmission through A1 R, which are enriched in glutamatergic terminals. Adenosine sharpens salience of information encoding in neuronal circuits: high-frequency stimulation triggers ATP release in the 'activated' synapse, which is locally converted by ecto-nucleotidases into adenosine to selectively activate A2A R; A2A R switch off A1 R and CB1 receptors, bolster glutamate release and NMDA receptors to assist increasing synaptic plasticity in the 'activated' synapse; the parallel engagement of the astrocytic syncytium releases adenosine further inhibiting neighboring synapses, thus sharpening the encoded plastic change...
December 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27337269/model-systems-for-platelet-receptor-shedding
#15
Markus Bender, David Stegner, Bernhard Nieswandt
Platelet adhesion and aggregation at sites of vascular injury are crucial for hemostasis; however, under pathological conditions, they can cause myocardial infarction and stroke. Platelet adhesion is mediated by binding of the glycoprotein (GP)Ib-V-IX complex to immobilized von Willebrand factor (vWF), thereby enabling the interaction of GPVI with exposed collagen and subsequent platelet activation. This process is reinforced by locally produced thrombin and platelet-derived adenosine diphosphate (ADP) and thromboxane A2 (TxA2), leading to a conformational change of integrins from a low- to a high-affinity state, which allows firm platelet adhesion and aggregation...
June 23, 2016: Platelets
https://www.readbyqxmd.com/read/27316550/hindbrain-estrogen-receptor-beta-antagonism-normalizes-reproductive-and-counter-regulatory-hormone-secretion-in-hypoglycemic-steroid-primed-ovariectomized-female-rats
#16
Karen P Briski, Prem K Shrestha
Hindbrain dorsal vagal complex A2 noradrenergic signaling represses the pre-ovulatory luteinizing hormone (LH) surge in response to energy deficiency. Insulin-induced hypoglycemia augments A2 neuron adenosine 5'-monophosphate-activated protein kinase (AMPK) activity and estrogen receptor-beta (ERβ) expression, coincident with LH surge suppression. We hypothesized that ERβ is critical for hypoglycemia-associated patterns of LH secretion and norepinephrine (NE) activity in key reproduction-relevant forebrain structures...
September 7, 2016: Neuroscience
https://www.readbyqxmd.com/read/27316329/leptin-suppresses-adenosine-triphosphate-induced-impairment-of-spinal-cord-astrocytes
#17
Baoman Li, Shuang Qi, Guangfeng Sun, Li Yang, Jidong Han, Yue Zhu, Maosheng Xia
Spinal cord injury (SCI) causes long-term disability and has no clinically effective treatment. After SCI, adenosine triphosphate (ATP) may be released from neuronal cells and astrocytes in large amounts. Our previous studies have shown that the extracellular release of ATP increases the phosphorylation of cytosolic phospholipase A2 (cPLA2 ) and triggers the rapid release of arachidonic acid (AA) and prostaglandin E2 (PGE2) via the stimulation of epidermal growth factor receptor (EGFR) and the downstream phosphorylation of extracellular-regulated protein kinases 1 and 2...
October 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27263955/the-effects-of-platelet-receptor-gpiib-iiia-polymorphism-leu-pro33-on-the-receptor-expression-and-platelet-aggregation-in-patients-with-ischaemic-stroke
#18
Endre Pongrácz, Katalin Schweitzer, József Furész, János Fent, Attila Tordai, Zoltán Nagy
Platelet hyperaggregation in ischaemic stroke patients is a proven finding, and associated with increased expression of the platelet surface GPIIb/IIIa receptor. The polymorphism occurs at nucleotide position 1565 of the GPIIIa gene resulting a 33Leu-Pro change. Data are conflicting regarding the abnormal function of the PlA1/A2 receptor in stroke. The aim of the study was to address the difference of platelet receptor function in ischemic stroke patients with the wild PlA1/A1 and heterozygous PlA1/A2 genotype...
December 5, 2007: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/27239843/-adenosine-a2a-receptor-as-a-drug-target-for-treatment-of-sepsis
#19
REVIEW
K V Sivak, A V Vasin, V V Egorov, V B Tsevtkov, N N Kuzmich, V A Savina, O I Kiselev
Sepsis is a generalized infection accompanied by response of the body that manifests in a clinical and laboratory syndrome, namely, in the systemic inflammatory response syndrome (SIRS) from the organism to the infection. Although sepsis is a widespread and life-threatening disease, the assortment of drugs for its treatment is mostly limited by antibiotics. Therefore, the search for new cellular targets for drug therapy of sepsis is an urgent task of modern medicine and pharmacology. One of the most promising targets is the adenosine A(2A) receptor (A(2A)AR)...
March 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27185496/contractile-effects-and-receptor-analysis-of-adenosine-receptors-in-human-detrusor-muscle-from-stable-and-neuropathic-bladders
#20
Mahreen Pakzad, Youko Ikeda, Carly McCarthy, Darryl G Kitney, Rita I Jabr, Christopher H Fry
To measure the relative transcription of adenosine receptor subtypes and the contractile effects of adenosine and selective receptor-subtype ligands on detrusor smooth muscle from patients with neuropathic overactive (NDO) and stable bladders and also from guinea-pigs. Contractile function was measured at 37°C in vitro from detrusor smooth muscle strips. Contractions were elicited by superfusate agonists or by electrical field stimulation. Adenosine-receptor (A1, A2A, A2B, A3) transcription was measured by RT-PCR...
August 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
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