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Purinergic signalling

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https://www.readbyqxmd.com/read/28087471/il-6-promotes-m2-macrophage-polarization-by-modulating-purinergic-signaling-and-regulates-the-lethal-release-of-nitric-oxide-during-trypanosoma-cruzi-infection
#1
Liliana M Sanmarco, Nicolás E Ponce, Laura M Visconti, Natalia Eberhardt, Martin G Theumer, Ángel R Minguez, Maria P Aoki
The production of nitric oxide (NO) is a key defense mechanism against intracellular pathogens but it must be tightly controlled in order to avoid excessive detrimental oxidative stress. In this study we described a novel mechanism through which interleukin (IL)-6 mediates the regulation of NO release induced in response to Trypanosoma cruzi infection. Using a murine model of Chagas disease, we found that, in contrast to C57BL/6 wild type (WT) mice, IL-6-deficient (IL6KO) mice exhibited a dramatic increase in plasma NO levels concomitant with a significantly higher amount of circulating IL-1β and inflammatory monocytes...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28069296/inflammatory-early-events-associated-to-the-role-of-p2x7-receptor-in-acute-murine-toxoplasmosis
#2
Gladys Corrêa, Carolina de Almeida Lindenberg, Aline Cristina de Abreu Moreira-Souza, Luiz Eduardo Baggio Savio, Christina Maeda Takiya, Camila Marques-da-Silva, Rossiane Claudia Vommaro, Robson Coutinho-Silva
Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7(-/-) mice are more susceptible than P2X7(+/+) mice to acute infection by the RH strain of T...
December 30, 2016: Immunobiology
https://www.readbyqxmd.com/read/28063919/proteomic-analysis-of-the-protective-effects-of-aqueous-bark-extract-of-terminalia-arjuna-roxb-on-isoproterenol-induced-cardiac-hypertrophy-in-rats
#3
Santosh Kumar, Md Jahangir Alam, Pankaj Prabhakar, Sayeed Ahmad, Subir K Maulik, Manish Sharma, Shyamal K Goswami
ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous bark extract of Terminalia arjuna (TA) has been in use as an ethnomedicine for cardiovascular ailments in the Indian subcontinent for centuries. Studies using hemodynamic, ROS scavenging and anti-inflammatory parameters in animal models have shown its anti-atherogenic, hypotensive, inotropic, anti-inflammatory effects. However, details analysis on its effects on established molecular and cell biological markers are a prerequisite for its wider acceptance to the medical community...
January 4, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28062289/evaluation-of-p2x7-receptor-expression-in-peripheral-lymphocytes-and-immune-profile-from-patients-with-indeterminate-form-of-chagas-disease
#4
Viviane do Carmo Gonçalves Souza, Joabel Tonellotto Dos Santos, Fernanda Licker Cabral, Fernanda Barbisan, Maria Isabel Azevedo, Luiz Felipe Dias Carli, Sonia de Avila Botton, Jeandre Augusto Dos Santos Jaques, Daniela Bitencourt Rosa Leal
Chagas disease (CD) is caused by Trypanosoma cruzi, an intracellular protozoan which is a potent stimulator of cell-mediated immunity. In the indeterminate form of CD (IFCD) a modulation between pro- and anti-inflammatory responses establishes a host-parasite adaptation. It was previously demonstrated that purinergic ecto-enzymes regulates extracellular ATP and adenosine levels, influencing immune and inflammatory processes during IFCD. In inflammatory sites ATP, as well as its degradation product, adenosine, function as signaling molecules and immunoregulators through the activation of purinergic receptors...
January 3, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28057794/purinergic-signaling-in-the-cardiovascular-system
#5
REVIEW
Geoffrey Burnstock
There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors...
January 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28039004/localized-inhibition-of-p2x7r-at-the-spinal-cord-injury-site-improves-neurogenic-bladder-dysfunction-by-decreasing-urothelial-p2x3r-expression-in-rats
#6
Alvaro Munoz, Iman K Yazdi, Xiufeng Tang, Carolina Rivera, Nima Taghipour, Robert G Grossman, Timothy B Boone, Ennio Tasciotti
AIMS: Reestablishment of bladder function in patients with spinal cord injury (SCI) is a clinical priority. Our objectives were to determine whether SCI-localized inhibition of purinergic P2X7 receptors (P2X7R) improve bladder function by decreasing afferent signals mediated by urothelial P2X3R. MAIN METHODS: Systemic inhibition of P2X7R may improve locomotion in rodent SCI models; however, beneficial effects on bladder function and its physiological mechanisms have not been evaluated...
December 27, 2016: Life Sciences
https://www.readbyqxmd.com/read/28038380/the-p2y2-nucleotide-receptor-is-an-inhibitor-of-vascular-calcification
#7
Shaomin Qian, Jenna N Regan, Maxwell T Shelton, April Hoggatt, Khalid S Mohammad, Paul B Herring, Cheikh I Seye
BACKGROUND AND AIMS: Mutations in the 5'-nucleotidase ecto (NT5E) gene that encodes CD73, a nucleotidase that converts AMP to adenosine, are linked to arterial calcification. However, the role of purinergic receptor signaling in the pathology of intimal calcification is not well understood. In this study, we examined whether extracellular nucleotides acting via P2Y2 receptor (P2Y2R) modulate arterial intimal calcification, a condition highly correlated with cardiovascular morbidity. METHODS: Apolipoprotein E, P2Y2R double knockout mice (ApoE(-/-)P2Y2R(-/-)) were used to determine the effect of P2Y2R deficiency on vascular calcification in vivo...
December 15, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28034895/impaired-aortic-contractility-to-uridine-adenosine-tetraphosphate-in-angiotensin-ii-induced-hypertensive-mice-receptor-desensitization
#8
Zhichao Zhou, Vishal R Yadav, Changyan Sun, Bunyen Teng, Jamal S Mustafa
OBJECTIVE: We previously showed that uridine adenosine tetraphosphate (Up4A)-mediated aortic contraction is partly mediated through purinergic P2X1 receptors (P2X1R). It has been reported that the plasma level of Up4A is elevated in hypertensive patients, implying a potential role for Up4A-P2X1R signaling in hypertension. This study investigated the vasoactive effect of Up4A in aortas isolated from angiotensin (Ang) II-infused (21 days) hypertensive mice. METHODS: Blood pressure was measured by tail cuff plethysmography...
December 29, 2016: American Journal of Hypertension
https://www.readbyqxmd.com/read/28030754/tonotopic-action-potential-tuning-of-maturing-auditory-neurons-through-endogenous-atp
#9
Saša Jovanovic, Tamara Radulovic, Claudio Coddou, Beatrice Dietz, Jana Nerlich, Stanko S Stojilkovic, Rudolf Rübsamen, Ivan Milenkovic
KEY POINTS: Following the genetically controlled formation of neuronal circuits, early firing activity guides the development of sensory maps in the auditory, visual and somatosensory system. However, it is not clear whether the activity of central auditory neurons is specifically regulated depending on the position within the sensory map. In the ventral cochlear nucleus, the first central station along the auditory pathway, we describe a mechanism through which paracrine ATP signalling enhances firing in a cell-specific and tonotopically-determined manner...
November 7, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#10
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
December 27, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/28011630/a-polycycstin-type-transient-receptor-potential-trp-channel-that-is-activated-by-atp
#11
David Traynor, Robert R Kay
ATP and ADP are ancient extra-cellular signalling molecules that in Dictyostelium amoebae cause rapid, transient increases in cytosolic calcium due to an influx through the plasma membrane. This response is independent of hetero-trimeric G-proteins, the putative IP3 receptor IplA and all P2X channels. We show, unexpectedly, that it is abolished in mutants of the polycystin-type transient receptor potential channel, TrpP. Responses to the chemoattractants cyclic-AMP and folic acid are unaffected in TrpP mutants...
December 23, 2016: Biology Open
https://www.readbyqxmd.com/read/28010756/deregulation-of-adenosine-receptors-in-psoriatic-epidermis-an-option-for-therapeutic-treatment
#12
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/28007536/conspecific-alarm-substance-differently-alters-group-behavior-of-zebrafish-populations-putative-involvement-of-cholinergic-and-purinergic-signaling-in-anxiety-and-fear-like-responses
#13
Julia Canzian, Barbara D Fontana, Vanessa A Quadros, Denis B Rosemberg
The zebrafish (Danio rerio) is an emergent model organism for assessing fear and anxiety-like phenotypes. The short fin wild type (WT), and leopard (leo) are two zebrafish populations that present several behavioral differences, in which leo displays pronounced defensive responses. Mounting evidence suggests a modulatory role for cholinergic and purinergic signaling in fear and anxiety, but the involvement of these neurotransmitter systems in the behavioral profile of zebrafish is obscure. Here we tested whether the acute exposure to conspecific alarm substance (AS), an experimental protocol that induces fear, alters shoaling behavior, diving response, acetylcholinesterase (AChE) activity, and nucleotide hydrolysis in brain tissue of WT and leo...
December 19, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27989503/a-purinergic-trail-for-metastases
#14
REVIEW
Davide Ferrari, Fabio Malavasi, Luca Antonioli
Nucleotides and nucleosides have emerged as important modulators of tumor biology. Recently acquired evidence shows that, when these molecules are released by cancer cells or surrounding tissues, they act as potent prometastatic factors, favoring tumor cell migration and tissue colonization. Therefore, nucleotides and nucleosides should be considered as a new class of prometastatic factors. In this review, we focus on the prometastatic roles of nucleotides and discuss future applications of purinergic signaling modulation in view of antimetastatic therapies...
December 15, 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27988461/divergent-regulatory-roles-of-extracellular-atp-in-the-degranulation-response-of-mouse-bone-marrow-derived-mast-cells
#15
Kazuki Yoshida, Masaaki Ito, Isao Matsuoka
Mast cells (MCs) play a critical role in allergic inflammation. Although purinergic signalling is implicated in the regulation of various immune responses, its role in MC function is not fully understood. In this study, we investigated the regulatory role of purinergic signalling in MC degranulation, using mouse bone marrow-derived mast cells (BMMCs). Notably, BMMCs expressed various functional P2 adenosine triphosphate (ATP) receptors, including ionotropic P2X4 and P2X7, involved in the regulation of BMMC degranulation...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27966087/signaling-pathways-underlying-the-antidepressant-like-effect-of-inosine-in-mice
#16
Filipe Marques Gonçalves, Vivian Binder Neis, Débora Kurrle Rieger, Mark William Lopes, Isabella A Heinrich, Ana Paula Costa, Ana Lúcia S Rodrigues, Manuella P Kaster, Rodrigo Bainy Leal
Inosine is a purine nucleoside formed by the breakdown of adenosine that elicits an antidepressant-like effect in mice through activation of adenosine A1 and A2A receptors. However, the signaling pathways underlying this effect are largely unknown. To address this issue, the present study investigated the influence of extracellular-regulated protein kinase (ERK)1/2, Ca(2+)/calmoduline-dependent protein kinase (CaMKII), protein kinase A (PKA), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase 3beta (GSK-3β) modulation in the antiimmobility effect of inosine in the tail suspension test (TST) in mice...
December 13, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27938989/geoff-burnstock-standing-down-from-editor-in-chief-position
#17
EDITORIAL
Michael P Gilbey
No abstract text is available yet for this article.
January 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/27936179/co2-induced-atp-dependent-release-of-acetylcholine-on-the-ventral-surface-of-the-medulla-oblongata
#18
Robert T R Huckstepp, Enrique Llaudet, Alexander V Gourine
Complex mechanisms that detect changes in brainstem parenchymal PCO2/[H+] and trigger adaptive changes in lung ventilation are responsible for central respiratory CO2 chemosensitivity. Previous studies of chemosensory signalling pathways suggest that at the level of the ventral surface of the medulla oblongata (VMS), CO2-induced changes in ventilation are (at least in part) mediated by the release and actions of ATP and/or acetylcholine (ACh). Here we performed simultaneous real-time biosensor recordings of CO2-induced ATP and ACh release from the VMS in vivo and in vitro, to test the hypothesis that central respiratory CO2 chemosensory transduction involves simultaneous recruitment of purinergic and cholinergic signalling pathways...
2016: PloS One
https://www.readbyqxmd.com/read/27935858/paradoxical-induction-of-growth-arrest-and-apoptosis-by-egf-via-the-up-regulation-of-pten-by-activating-redox-factor-1-egr-1-in-human-lung-cancer-cells
#19
Je-Won Ryu, Sung Sik Choe, Seung-Hee Ryu, Eun-Young Park, Byoung Wook Lee, Tae Keun Kim, Chang Hoon Ha, Sang-Wook Lee
Epidermal growth factor (EGF) signaling promotes cell proliferation and survival in several types of cancer. Here, however, we showed that EGF inhibits proliferation and promotes programmed cell death in non-small cell lung cancer (NSCLC) cells. In A549 cells, EGF increased redox factor-1 (Ref-1) expression and the association of Ref-1 with zinc finger-containing transcriptional regulator (EGR1) via activation of p22phox, RAC1, and an NADPH oxidase subunit. EGF increased p22phox and RAC1 expression through activation of purinergic receptors (P2Y)...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27934233/modeling-membrane-protein-ligand-binding-interactions-the-human-purinergic-platelet-receptor
#20
D'Artagnan Greene, Wesley M Botello-Smith, Alec Follmer, Li Xiao, Eleftherios Lambros, Ray Luo
Membrane proteins, due to their roles as cell receptors and signaling mediators, make prime candidates for drug targets. The computational analysis of protein-ligand binding affinities has been widely employed as a tool in rational drug design efforts. Although efficient implicit solvent-based methods for modeling globular protein-ligand binding have been around for many years, the extension of such methods to membrane protein-ligand binding is still in its infancy. In this study, we extended the widely used Amber/MMPBSA method to model membrane protein-ligand systems, and we used it to analyze protein-ligand binding for the human purinergic platelet receptor (P2Y12R), a prominent drug target in the inhibition of platelet aggregation for the prevention of myocardial infarction and stroke...
December 8, 2016: Journal of Physical Chemistry. B
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