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Purinergic signalling

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https://www.readbyqxmd.com/read/28900295/an-autocrine-purinergic-signaling-controls-astrocyte-induced-neuronal-excitation
#1
Weida Shen, Ljiljana Nikolic, Claire Meunier, Frank Pfrieger, Etienne Audinat
Astrocyte-derived gliotransmitters glutamate and ATP modulate neuronal activity. It remains unclear, however, how astrocytes control the release and coordinate the actions of these gliotransmitters. Using transgenic expression of the light-sensitive channelrhodopsin 2 (ChR2) in astrocytes, we observed that photostimulation reliably increases action potential firing of hippocampal pyramidal neurons. This excitation relies primarily on a calcium-dependent glutamate release by astrocytes that activates neuronal extra-synaptic NMDA receptors...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899893/acute-in-vivo-analysis-of-atp-release-in-rat-kidneys-in-response-to-changes-of-renal-perfusion-pressure
#2
Oleg Palygin, Louise C Evans, Allen W Cowley, Alexander Staruschenko
BACKGROUND: ATP and derivatives are recognized to be essential agents of paracrine signaling. It was reported that ATP is an important regulator of the pressure-natriuresis mechanism. Information on the sources of ATP, the mechanisms of its release, and its relationship to blood pressure has been limited by the inability to precisely measure dynamic changes in intrarenal ATP levels in vivo. METHODS AND RESULTS: Newly developed amperometric biosensors were used to assess alterations in cortical ATP concentrations in response to changes in renal perfusion pressure (RPP) in anesthetized Sprague-Dawley rats...
September 12, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28898552/a-key-tyrosine-substitution-restricts-nucleotide-hydrolysis-by-the-ectoenzyme-npp5
#3
Alexei Gorelik, Antsa Randriamihaja, Katalin Illes, Bhushan Nagar
The ecto-nucleotide pyrophosphatase / phosphodiesterase (NPP) family of proteins mediates purinergic signaling by degrading extracellular nucleotides, and also participates in phospholipid metabolism. NPP5 (ENPP5) is the least characterized member of this group and its specific role is unknown. This enzyme does not display activity on certain nucleotides and on other typical NPP substrates. In order to gain insights into its function, we determined the crystal structure of human and murine NPP5. Structural comparison with close homologs revealed a key phenylalanine to tyrosine substitution that prevents efficient hydrolysis of nucleotide diphosphates and triphosphates; reversal of this mutation enabled degradation of these molecules...
September 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28898282/p2x3-receptor-involvement-in-endometriosis-pain-via-erk-signaling-pathway
#4
Shaojie Ding, Libo Zhu, Yonghong Tian, Tianhong Zhu, Xiufeng Huang, Xinmei Zhang
The purinergic receptor P2X ligand-gated ion channel 3 (P2X3) is crucially involved in peripheral nociceptive processes of somatic and visceral pain. Endometriosis pain is considered as a kind of inflammatory and neuropathic pain. However, whether P2X3 is involved in endometriosis pain has not been reported up to date. Here, we aimed to determine whether P2X3 expression in endometriotic lesions is involved in endometriosis pain, which is regulated by inflammatory mediators through extracellular regulated protein kinases (ERK) signalling pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28886985/pannexin-1-channels-in-epilepsy
#5
REVIEW
Mark S Aquilino, Paige Whyte-Fagundes, Georg Zoidl, Peter L Carlen
Pannexin-1 (Panx1) expression is raised in several animal seizure models and in resected human epileptic brain tissue, suggesting relevance to epilepsy. Multiple factors that are characteristic of seizures are thought to regulate Panx1 channel opening, including elevated levels of extracellular K(+). Panx1, when open, 1) releases ATP, glutamate, and other metabolites into the extracellular medium, and 2) may depolarize the membrane due to a channel reversal potential around 0mV. Resultant ATP release from stimulated Panx1 can activate purinergic receptors, including P2X7 receptors...
September 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28884198/mouse-pancreatic-islet-macrophages-use-locally-released-atp-to-monitor-beta-cell-activity
#6
Jonathan R Weitz, Madina Makhmutova, Joana Almaça, Julia Stertmann, Kristie Aamodt, Marcela Brissova, Stephan Speier, Rayner Rodriguez-Diaz, Alejandro Caicedo
AIMS/HYPOTHESIS: Tissue-resident macrophages sense the microenvironment and respond by producing signals that act locally to maintain a stable tissue state. It is now known that pancreatic islets contain their own unique resident macrophages, which have been shown to promote proliferation of the insulin-secreting beta cell. However, it is unclear how beta cells communicate with islet-resident macrophages. Here we hypothesised that islet macrophages sense changes in islet activity by detecting signals derived from beta cells...
September 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28879644/adenosine-reduces-reactive-oxygen-species-and-interleukin-8-production-by-trichomonas-vaginalis-stimulated-neutrophils
#7
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/28870136/ectonucleotidase-inhibitors-a-patent-review-2011-2016
#8
Mariya Al-Rashida, Syeda Uroos Qazi, Nayab Batool, Abdul Hameed, Jamshed Iqbal
Ectonucleotidases are a broad family of metallo-ectoenzymes that are responsible for hydrolysing a variety of nucleotides to nucleosides, hence orchestrating the activation of P1 and P2 cell receptors via controlled release of nucleotides and nucleosides. Many disorders such as impaired calcification including aortic calcification, neurological and immunological disorders, platelet aggregation, cell proliferation and metastasis. are characterized by an increase in expression of these ectonucleotidases. Consequently, selective inhibitors of ectonucleotidases are required for therapeutic intervention...
September 5, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28863817/regulation-of-p2x-purinergic-receptor-signaling-by-cholesterol
#9
Ruth D Murrell-Lagnado
P2X receptors are cation-selective channels that are activated by the binding of extracellular ATP. They have a high permeability to Ca(2+), Na(+), and K(+) and are expressed widely throughout the nervous, immune, cardiovascular, skeletal, gastrointestinal, respiratory, and endocrine systems. Seven mammalian subtypes of P2X receptor subunits have been identified, P2X1-7, and those that function as homotrimeric receptors (P2X1, 2, 3, 4, and 7) are targeted to lipid rafts, although they show limited resistance to solubilization by Triton X-100...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28860068/protraction-of-neuropathic-pain-by-morphine-is-mediated-by-spinal-damage-associated-molecular-patterns-damps-in-male-rats
#10
Peter M Grace, Keith A Strand, Erika L Galer, Kenner C Rice, Steven F Maier, Linda R Watkins
We have recently reported that a short course of morphine, starting 10days after sciatic chronic constriction injury (CCI), prolonged the duration of mechanical allodynia for months after morphine ceased. Maintenance of this morphine-induced persistent sensitization was dependent on spinal NOD-like receptor protein 3 (NLRP3) inflammasomes-protein complexes that proteolytically activate interleukin-1β (IL-1β) via caspase-1. However, it is still unclear how NLRP3 inflammasome signaling is maintained long after morphine is cleared...
August 30, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28857186/anti-schistosome-antibodies-change-ntpdase-1-activity-from-macrophages
#11
Danielle Gomes Marconato, Michélia Antônia do Nascimento Gusmão, Juliana Melo, Juciane Maria de Andrade Castro, Gilson Costa Macedo, Eveline Gomes Vasconcelos, Priscila de Faria-Pinto
NTPDases are enzymes that hydrolyze di- and tri-phosphate nucleosides, regulating purinergic signaling in many organisms. The Schistosoma mansoni NTPDases, SmATPDases 1 and 2 are antigenic proteins and display a significant homology with the isoforms found in mammalian cells. In this work, we investigated whether anti-SmATPDase antibodies from S. mansoni-infected mice sera show cross-reactivity with the NTPDase 1 isoform from macrophages and how this event affect the cell proliferation. By Western blot, anti-SmATPDase antibodies present in serum from infected mice recognized two bands with approximately 53 and 58 kDa, corresponding to NTPDase 1...
August 30, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28836401/purinergic-receptor-expression-and-potential-association-with-human-embryonic-stem-cell-derived-oligodendrocyte-progenitor-cell-development
#12
Shirin Kashfi, Maryam Peymani, Kamran Ghaedi, Hossein Baharvand, Mohammad Hossein Nasr-Esfahani, Mohammad Javan
OBJECTIVES: Due to recent progress in production of human embryonic stem cell-derived oligodendrocyte progenitor cells (hESC-OPCs) for ameliorating myelin disease such as multiple sclerosis (MS) and the role of purinergic signaling in OPCs development, we avaluated the profile of purinergic receptors expression during development of OPCs from hESC. MATERIALS AND METHODS: In this experimental study, we used reverse transcription and quantitative polymerase chain reaction (RT-qPCR) to obtain more information about potential roles of purinergic receptors during in vitro production of hESC-OPCs...
October 2017: Cell Journal
https://www.readbyqxmd.com/read/28828576/bone-turnover-is-altered-in-transgenic-rats-overexpressing-the-p2y2-purinergic-receptor
#13
Maria Ellegaard, Cansu Agca, Solveig Petersen, Ankita Agrawal, Lars Schack Kruse, Ning Wang, Alison Gartland, Jens-Erik Beck Jensen, Niklas Rye Jørgensen, Yuksel Agca
It is now widely recognized that purinergic signaling plays an important role in the regulation of bone remodeling. One receptor subtype, which has been suggested to be involved in this regulation, is the P2Y2 receptor (P2Y2R). In the present study, we investigated the effect of P2Y2R overexpression on bone status and bone cell function using a transgenic rat. Three-month-old female transgenic Sprague Dawley rats overexpressing P2Y2R (P2Y2R-Tg) showed higher bone strength of the femoral neck. Histomorphometry showed increase in resorptive surfaces and reduction in mineralizing surfaces...
August 21, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28827203/identification-of-novel-gpr17-agonists-by-structural-bioinformatics-and-signaling-activation
#14
Konda Mani Saravanan, Suresh Palanivel, Olli Yli-Harja, Meenakshisundaram Kandhavelu
G Protein-coupled Receptor 17 (GPR17) is phylogenetically related to the purinergic receptors emerged as a potential drug target for multiple sclerosis, Parkinson disease, Alzheimer disease and cancer. Unfortunately, the crystal structure of GPR17 is unresolved. With the interest in structure-based ligand discovery, we modeled the structure of GPR17. The model allowed us to identify two novel agonists, AC1MLNKK and T0510.3657 that selectively activate GPR17 which exhibit better interaction properties than previously known ligand, MDL29951...
August 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28822016/in-situ-imaging-reveals-properties-of-purinergic-signalling-in-trigeminal-sensory-ganglia-in-vitro
#15
Arletta Nowodworska, Arn M J M van den Maagdenberg, Andrea Nistri, Elsa Fabbretti
Chronic pain is supported by sterile inflammation that induces sensitisation of sensory neurons to ambient stimuli including extracellular ATP acting on purinergic P2X receptors. The development of in vitro methods for drug screening would be useful to investigate cell crosstalk and plasticity mechanisms occurring during neuronal sensitisation and sterile neuroinflammation. Thus, we studied, at single-cell level, membrane pore dilation based on the uptake of a fluorescent probe following sustained ATP-gated P2X receptor function in neurons and non-neuronal cells of trigeminal ganglion cultures from wild-type (WT) and R192Q CaV2...
August 18, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28815512/p2y2-receptor-functions-in-cancer-a-perspective-in-the-context-of-colorectal-cancer
#16
Fernand-Pierre Gendron, Morgane Placet, Guillaume Arguin
Purinergic signaling has recently emerged as a network of signaling molecules, enzymes and receptors that coordinates the action and behavior of cancerous cells. Extracellular adenosine 5' triphosphate activates a plethora of P2 nucleotide receptors that can putatively modulate cancer cell proliferation, survival and dissemination. In this context, the G protein-coupled P2Y2 receptor was identified as one of the entities coordinating the cellular and molecular events that characterize cancerous cells. In this chapter, we will look at the contribution of the P2Y2 receptor in cancer outcomes and use this information to demonstrate that the P2Y2 receptor represents a drug target of interest in the setting of colorectal cancer, for which the role and function of this receptor is poorly defined...
August 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28809765/cyclin-dependent-kinase-5-modulates-the-p2x2a-receptor-channel-gating-through-phosphorylation-of-c-terminal-threonine-372
#17
Claudio Coddou, Rodrigo Sandoval, Patricio Castro, Pablo Lazcano, Maria José Hevia, Milos Rokic, Bradford Hall, Anita Terse, Christian Gonzalez-Billault, Ashok B Kulkarni, Stanko S Stojilkovic, Elias Utreras
The purinergic P2X2 receptor (P2X2R) is an adenosine triphosphate-gated ion channel widely expressed in the nervous system. Here, we identified a putative cyclin-dependent kinase 5 (Cdk5) phosphorylation site in the full-size variant P2X2aR (TPKH), which is absent in the splice variant P2X2bR. We therefore investigated the effects of Cdk5 and its neuronal activator, p35, on P2X2aR function. We found an interaction between P2X2aR and Cdk5/p35 by co-immunofluorescence and co-immunoprecipitation in HEK293 cells...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28808008/mathematical-model-reveals-role-of-nucleotide-signaling-in-airway-surface-liquid-homeostasis-and-its-dysregulation-in-cystic-fibrosis
#18
Conner I Sandefur, Richard C Boucher, Timothy C Elston
Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28791515/a-multiscale-fluidic-device-for-the-study-of-dendrite-mediated-cell-to-cell-communication
#19
Sean McCutcheon, Robert Majeska, Mitchell Schaffler, Maribel Vazquez
Many cell types communicate by means of dendritic extensions via a multi-tiered set of geometric and chemical cues. Until recently, mimicking the compartmentalized in vivo cellular environment of dendrite-expressing cells such as osteocytes and motor neurons in a spatially and temporally controllable manner was limited by the challenges of in vitro device fabrication at submicron scales. Utilizing the improved resolution of current fabrication technology, we have designed a multiscale device, the Macro-micro-nano system, or Mμn, composed of two distinct cell-seeding and interrogation compartments separated by a nanochannel array...
August 8, 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28791020/p2x7-receptor-induces-tumor-necrosis-factor-%C3%AE-converting-enzyme-activation-and-release-to-boost-tnf-%C3%AE-production
#20
Maria Barberà-Cremades, Ana I Gómez, Alberto Baroja-Mazo, Laura Martínez-Alarcón, Carlos M Martínez, Carlos de Torre-Minguela, Pablo Pelegrín
Tumor necrosis factor (TNF)-α is a major pro-inflammatory cytokine produced in response to toll-like receptor stimulation. TNF-α release is controlled by the activity of TNF-α converting enzyme (TACE) that cut membrane-bound TNF-α to shed its ectodomain as a soluble cytokine. The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is activated in response to elevated concentrations of extracellular ATP and induces different pro-inflammatory pathways in macrophages to establish an inflammatory response...
2017: Frontiers in Immunology
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