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Purinergic Signalling

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https://www.readbyqxmd.com/read/29349673/pharmacological-dissection-of-the-cellular-mechanisms-associated-to-the-spontaneous-and-the-mechanically-stimulated-atp-release-by-mesentery-endothelial-cells-roles-of-thrombin-and-trpv
#1
M Verónica Donoso, Felipe Hernández, Tania Villalón, Claudio Acuña-Castillo, J Pablo Huidobro-Toro
Endothelial cells participate in extracellular ATP release elicited by mechanosensors. To characterize the dynamic interactions between mechanical and chemical factors that modulate ATP secretion by the endothelium, we assessed and compared the mechanisms participating in the spontaneous (basal) and mechanically stimulated secretion using primary cultures of rat mesentery endothelial cells. ATP/metabolites were determined in the cell media prior to (basal) and after cell media displacement or a picospritzer buffer puff used as mechanical stimuli...
January 19, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29332180/cd39-adenosinergic-axis-in-renal-pathophysiology-and-therapeutics
#2
REVIEW
Bellamkonda K Kishore, Simon C Robson, Karen M Dwyer
Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis...
January 13, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29322373/epac-is-required-for-exogenous-and-endogenous-stimulation-of-adenosine-a2b-receptor-for-inhibition-of-angiotensin-ii-induced-collagen-synthesis-and-myofibroblast-differentiation
#3
Sarawuth Phosri, Kwanchai Bunrukchai, Warisara Parichatikanond, Vilasinee H Sato, Supachoke Mangmool
Angiotensin II (Ang II) plays an important role on the pathogenesis of cardiac fibrosis. Prolong and overstimulation of angiotensin II type 1 receptor with Ang II-induced collagen synthesis and myofibroblast differentiation in cardiac fibroblasts, leading to cardiac fibrosis. Although adenosine and its analogues are known to have cardioprotective effects, the mechanistic by which adenosine A2 receptors (A2Rs) inhibit Ang II-induced cardiac fibrosis is not clearly understood. In the present study, we examined the effects of exogenous adenosine and endogenous adenosine on Ang II-induced collagen and myofibroblast differentiation determined by α-smooth muscle action (α-SMA) overexpression and their underlying signal transduction...
January 10, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29290027/n-terminal-tagging-of-human-p2x7-receptor-disturbs-calcium-influx-and-dye-uptake
#4
Karin Dreisig, Nikolaj Pagh Kristensen, Maja Wallentin Dommer, Niklas Rye Jørgensen, Birgitte Rahbek Kornum
The P2X7 receptor is a frequently studied member of the purinergic receptor family signalling via channel opening and membrane pore formation. Fluorescent imaging is an important molecular method for studying cellular receptor expression and localization. Fusion of receptors to fluorescent proteins might cause major functional changes and requires careful functional evaluation such as has been done for the rat P2X7 receptor. This study examines fusion constructs of the human P2X7 receptor. We assessed surface expression, channel opening with calcium influx, and pore formation using YO-PRO-1 dye uptake in response to BzATP stimulation in transfected cells...
December 30, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29236227/loss-of-vascular-expression-of-nucleoside-triphosphate-diphosphohydrolase-1-cd39-in-hypertension
#5
Charlotte Roy, Julie Tabiasco, Antoine Caillon, Yves Delneste, Jean Merot, Julie Favre, Anne Laure Guihot, Ludovic Martin, Daniele C Nascimento, Bernhard Ryffel, Simon C Robson, Jean Sévigny, Daniel Henrion, Gilles Kauffenstein
Ectonucleoside triphosphate diphosphohydrolase-1, the major vascular/immune ectonucleotidase, exerts anti-thrombotic and immunomodulatory actions by hydrolyzing extracellular nucleotides (danger signals). Hypertension is characterized by vascular wall remodeling, endothelial dysfunction, and immune infiltration. Here our aim was to investigate the impact of arterial hypertension on CD39 expression and activity in mice. Arterial expression of CD39 was determined by reverse transcription quantitative real-time PCR in experimental models of hypertension, including angiotensin II (AngII)-treated mice (1 mg/kg/day, 21 days), deoxycorticosterone acetate-salt mice (1% salt and uninephrectomy, 21 days), and spontaneously hypertensive rats...
December 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29188550/udp-induced-relaxation-is-enhanced-in-aorta-from-female-obese-otsuka-long-evans-tokushima-fatty-rats
#6
Shota Kobayashi, Takayuki Matsumoto, Makoto Ando, Maika Iguchi, Shun Watanabe, Kumiko Taguchi, Tsuneo Kobayashi
Uridine 5'-diphosphate (UDP) plays an important role in controlling vascular tone; however, UDP-mediated response in metabolic syndromes, including obesity and type 2 diabetes in females, remains unclear. In this study, we investigated UDP-mediated response in the aorta of female obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF rat aortas precontracted by phenylephrine (PE) (vs. LETO), (1) UDP-induced relaxation was increased, whereas acetylcholine (ACh)-induced relaxation was decreased; (2) no UDP- or ACh-induced relaxations were observed in endothelial denudation, whereas UDP-induced small contraction was observed; and (3) NG-nitro-L-arginine [L-NNA, a nitric oxide (NO) synthase inhibitor] eliminated UDP-induced relaxation and small contraction, whereas caused contrasting responses by ACh, including slight relaxations (LETO) and contractions (OLETF)...
November 29, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29170977/species-differences-and-mechanism-of-action-of-a3-adenosine-receptor-allosteric-modulators
#7
Lili Du, Zhan-Guo Gao, Silvia Paoletta, Tina C Wan, Elizabeth T Gizewski, Samantha Barbour, Jacobus P D van Veldhoven, Adriaan P IJzerman, Kenneth A Jacobson, John A Auchampach
Activity of the A3 adenosine receptor (AR) allosteric modulators LUF6000 (2-cyclohexyl-N-(3,4-dichlorophenyl)-1H-imidazo [4,5-c]quinolin-4-amine) and LUF6096 (N-{2-[(3,4-dichlorophenyl)amino]quinolin-4-yl}cyclohexanecarbox-amide) was compared at four A3AR species homologs used in preclinical drug development. In guanosine 5'-[γ-[(35)S]thio]triphosphate ([(35)S]GTPγS) binding assays with cell membranes isolated from human embryonic kidney cells stably expressing recombinant A3ARs, both modulators substantially enhanced agonist efficacy at human, dog, and rabbit A3ARs but provided only weak activity at mouse A3ARs...
November 23, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29022161/pom-1-inhibits-p2-receptors-and-exhibits-anti-inflammatory-effects-in-macrophages
#8
Gabriela Pimenta-Dos-Reis, Eduardo José Lopes Torres, Paula Gabriela Quintana, Lincon Onorio Vidal, Bárbara Andréa Fortes Dos Santos, Chuan-Sheng Lin, Norton Heise, Pedro Muanis Persechini, Julieta Schachter
Extracellular nucleotides can modulate the immunological response by activating purinergic receptors (P2Rs) on the cell surface of macrophages, dendritic, and other immune cells. In particular, the activation of P2X7R can induce release of cytokines and cell death as well as the uptake of large molecules through the cell membrane by a mechanism still poorly understood. Polyoxotungstate-1 (POM-1) has been proposed as a potent inhibitor of ecto-nucleotidases, enzymes that hydrolyze extracellular nucleotides, regulating the activity of P2Rs...
December 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29164451/the-potential-of-p2x7-receptors-as-a-therapeutic-target-including-inflammation-and-tumour-progression
#9
REVIEW
Geoffrey Burnstock, Gillian E Knight
Seven P2X ion channel nucleotide receptor subtypes have been cloned and characterised. P2X7 receptors (P2X7R) are unusual in that there are extra amino acids in the intracellular C terminus. Low concentrations of ATP open cation channels sometimes leading to cell proliferation, whereas high concentrations of ATP open large pores that release inflammatory cytokines and can lead to apoptotic cell death. Since many diseases involve inflammation and immune responses, and the P2X7R regulates inflammation, there has been recent interest in the pathophysiological roles of P2X7R and the potential of P2X7R antagonists to treat a variety of diseases...
November 21, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29159762/p2y12-receptor-upregulation-in-satellite-glial-cells-is-involved-in-neuropathic-pain-induced-by-hiv-glycoprotein-120-and-2-3-dideoxycytidine
#10
Zhihua Yi, Lihui Xie, Congfa Zhou, Huilong Yuan, Shuai Ouyang, Zhi Fang, Shanhong Zhao, Tianyu Jia, Lifang Zou, Shouyu Wang, Yun Xue, Bing Wu, Yun Gao, Guilin Li, Shuangmei Liu, Hong Xu, Changshui Xu, Chunping Zhang, Shangdong Liang
The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine)...
November 20, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29134411/distinct-roles-of-ecto-nucleoside-triphosphate-diphosphohydrolase-2-ntpdase2-in-liver-regeneration-and-fibrosis
#11
Linda Feldbrügge, Z Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Stephanie Tran, Eric U Yee, Sonja Rothweiler, Kahini A Vaid, Jean Sévigny, Moritz Schmelzle, Yury V Popov, Simon C Robson
Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) are cell surface-located transmembrane ecto-enzymes of the CD39 superfamily which regulate inflammation and tissue repair by catalyzing the phosphohydrolysis of extracellular nucleotides and modulating purinergic signaling. In the liver, NTPDase2 is reportedly expressed on portal fibroblasts, but its functional role in regulating tissue regeneration and fibrosis is incompletely understood. Here, we studied the role of NTPDase2 in several models of liver injury using global knockout mice...
November 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29116551/anti-inflammatory-effect-of-a-novel-locally-acting-a2a-receptor-agonist-in-a-rat-model-of-oxazolone-induced-colitis
#12
L Antonioli, A El-Tayeb, C Pellegrini, M Fornai, O Awwad, G Giustarini, G Natale, L Ryskalin, Z H Németh, C E Müller, C Blandizzi, R Colucci
Adenosine represents a powerful modulating factor, which has been shown to orchestrate the scope, duration, and remission of the inflammatory response through the activation of four specific receptors, classified as A1, A2A, A2B, and A3, all being widely expressed in a variety of immune cells. Several selective A2A receptor agonists have displayed anti-inflammatory effects, through the suppression of IL-12, TNF, and IFN-γ production by monocytes and lymphocytes, in the setting of chronic intestinal inflammation...
November 8, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29086245/myeloid-p2y2-receptor-promotes-acute-inflammation-but-is-dispensable-for-chronic-high-fat-diet-induced-metabolic-dysfunction
#13
Samantha E Adamson, Garren Montgomery, Scott A Seaman, Shayn M Peirce-Cottler, Norbert Leitinger
The purinergic receptor P2Y2 binds ATP to control chemotaxis of myeloid cells, and global P2Y2 receptor knockout mice are protected in models of acute inflammation. Chronic inflammation mediated by macrophages and other immune cells in adipose tissue contributes to the development of insulin resistance. Here, we investigate whether mice lacking P2Y2 receptors on myeloid cells are protected against acute and chronic inflammation. Wild-type mice were transplanted with either wild-type or P2Y2 receptor null bone marrow and treated with a sublethal dose of endotoxin as a model of acute inflammation, or fed a high-fat diet to induce obesity and insulin resistance as a model of chronic inflammation...
October 30, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28956227/various-n-glycoforms-differentially-upregulate-e-ntpdase-activity-of-the-ntpdase3-cd39l3-ecto-enzymatic-domain
#14
Alexander H Zhong, Z Gordon Jiang, Richard D Cummings, Simon C Robson
The GDA1/CD39 ecto-nucleoside triphosphate diphosphosphohydrolase (E-NTPDase) superfamily is a group of eight heavily glycosylated ecto-enzymes that hydrolyze extracellular nucleosides di- and tri-phosphates in the presence of divalent cations, to generate the monophosphate derivatives. This catalytic process differentially regulates a complex array of purinergic signaling responses. NTPDase3/CD39L3is dominantly expressed in pancreatic islet cells, where it may regulate insulin secretion, and has seven N-linked glycosylation sites with four close to five highly conserved domains called "apyrase conserved regions" (ACRs)...
September 27, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28929376/divergent-coronary-flow-responses-to-uridine-adenosine-tetraphosphate-in-atherosclerotic-apoe-knockout-mice
#15
Bunyen Teng, Hicham Labazi, Changyan Sun, Yan Yang, Xiaorong Zeng, S Jamal Mustafa, Zhichao Zhou
Uridine adenosine tetraphosphate (Up4A) exerts potent relaxation in porcine coronary arteries that is reduced following myocardial infarction, suggesting a crucial role for Up4A in the regulation of coronary flow (CF) in cardiovascular disorders. We evaluated the vasoactive effects of Up4A on CF in atherosclerosis using ApoE knockout (KO) mice ex vivo and in vivo. Functional studies were conducted in isolated mouse hearts using the Langendorff technique. Immunofluorescence was performed to assess purinergic P2X1 receptor (P2X1R) expression in isolated mouse coronary arteries...
September 20, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28905300/p2x7r-antagonism-after-subfailure-overstretch-injury-of-blood-vessels-reverses-vasomotor-dysfunction-and-prevents-apoptosis
#16
Weifeng Luo, Daniel Feldman, Reid McCallister, Colleen Brophy, Joyce Cheung-Flynn
Human saphenous vein (HSV) is harvested and prepared prior to implantation as an arterial bypass graft. Injury and the response to injury from surgical harvest and preparation trigger cascades of molecular events and contribute to graft remodeling and intimal hyperplasia. Apoptosis is an early response after implantation that contributes the development of neointimal lesions. Here, we showed that surgical harvest and preparation of HSV leads to vasomotor dysfunction, increased apoptosis and downregulation of the phosphorylation of the anti-apoptotic protein, Niban...
September 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28895091/abstracts-from-the-2017-italian-german-purine-club-meeting
#17
(no author information available yet)
No abstract text is available yet for this article.
September 11, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28879644/adenosine-reduces-reactive-oxygen-species-and-interleukin-8-production-by-trichomonas-vaginalis-stimulated-neutrophils
#18
Amanda Piccoli Frasson, Camila Braz Menezes, Gustavo Krumel Goelzer, Simone Cristina Baggio Gnoatto, Solange Cristina Garcia, Tiana Tasca
Trichomonas vaginalis is a flagellated protozoan that affects the human urogenital tract causing 276.4 million new infections a year. The parasite elicits a vaginal mucosal infiltration of immune cells, especially neutrophils which are considered to be primarily responsible for cytological change observed at the infection site as well as the major contributor in the inflammatory response against the parasite. Extracellular nucleotides and their nucleosides are signaling compounds involved in several biological processes, including inflammation and immune responses...
September 6, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28875249/from-the-7th-joint-italian-german-purine-club-meeting-to-european-purine-club-meetings
#19
EDITORIAL
Felicita Pedata
No abstract text is available yet for this article.
September 5, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28555330/the-p2y1-receptor-mediated-leukocyte-adhesion-to-endothelial-cells-is-inhibited-by-melatonin
#20
Tassya Cataldi Cardoso, Thaís Emanuelle Pompeu, Claudia Lucia Martins Silva
Extracellular ATP (released by endothelial and immune cells) and its metabolite ADP are important pro-inflammatory mediators via the activation of purinergic P2 receptors (P2Y and P2X), which represent potential new targets for anti-inflammatory therapy. Endothelial P2Y1 receptor (P2Y1R) induces endothelial cell activation triggering leukocyte adhesion. A number of data have implicated melatonin as a modulator of immunity, inflammation, and endothelial cell function, but to date no studies have investigated whether melatonin modulates endothelial P2YR signaling...
September 2017: Purinergic Signalling
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