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Purinergic signalling

Mengjie Lu, Beili Wu
G protein-coupled receptors (GPCRs) comprise the largest membrane protein family. These receptors sense a variety of signaling molecules, activate multiple intracellular signal pathways, and act as the targets of over 40% of marketed drugs. Recent progress on GPCR structural studies provides invaluable insights into the structure-function relationship of the GPCR superfamily, deepening our understanding about the molecular mechanisms of GPCR signal transduction. Here, we review recent breakthroughs on GPCR structure determination and the structural features of GPCRs, and take the structures of chemokine receptor CCR5 and purinergic receptors P2Y1 R and P2Y12 R as examples to discuss the importance of GPCR structures on functional studies and drug discovery...
October 20, 2016: IUBMB Life
Michael J Osgood, Kevin Sexton, Igor Voskresensky, Kyle Hocking, Jun Song, Padmini Komalavilas, Colleen Brophy, Joyce Cheung-Flynn
BACKGROUND: Intimal hyperplasia remains the primary cause of vein graft failure for the 1 million yearly bypass procedures performed using human saphenous vein (HSV) grafts. This response to injury is caused in part by the harvest and preparation of the conduit. The use of Brilliant Blue FCF (FCF) restores injury-induced loss of function in vascular tissues possibly via inhibition of purinergic receptor signaling. This study investigated whether pretreatment of the vein graft with FCF prevents intimal hyperplasia...
August 2016: Journal of Vascular Surgery
Andreas Reichenbach, Andreas Bringmann
Müller glia, the principal macroglia of the retina, express diverse subtypes of adenosine and metabotropic purinergic (P2Y) receptors. Müller cells of several species, including man, also express ionotropic P2X7 receptors. ATP is liberated from Müller cells after activation of metabotropic glutamate receptors and during osmotic and mechanical induction of membrane stretch; adenosine is released through equilibrative nucleoside transporters. Müller cell-derived purines modulate the neuronal activity and have autocrine effects, for example, induction of glial calcium waves and regulation of the cellular volume...
October 2016: Journal of Ocular Pharmacology and Therapeutics
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
Lien M Dos Santos, Tatiane M da Silva, Juliana H Azambuja, Priscila T Ramos, Pathise S Oliveira, Elita F da Silveira, Nathalia S Pedra, Kennia Galdino, Carlus A T do Couto, Mayara S P Soares, Rejane G Tavares, Roselia M Spanevello, Francieli M Stefanello, Elizandra Braganhol
Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established...
October 17, 2016: Molecular and Cellular Biochemistry
Luiz Eduardo Baggio Savio, Mariana G Juste Andrade, Paola de Andrade Mello, Patrícia Teixeira Santana, Aline Cristina Abreu Moreira-Souza, Janaína Kolling, Aline Longoni, Linda Feldbrügge, Yan Wu, Angela T S Wyse, Simon C Robson, Robson Coutinho-Silva
Sepsis results in unfettered inflammation, tissue damage, and multiple organ failure. Diffuse brain dysfunction and neurological manifestations secondary to sepsis are termed sepsis-associated encephalopathy (SAE). Extracellular nucleotides, proinflammatory cytokines, and oxidative stress reactions are associated with delirium and brain injury, and might be linked to the pathophysiology of SAE. P2X7 receptor activation by extracellular ATP leads to maturation and release of IL-1β by immune cells, which stimulates the production of oxygen reactive species...
October 11, 2016: Molecular Neurobiology
Andrew Keech, Ute Vollmer-Conna, Benjamin K Barry, Andrew R Lloyd
Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown pathogenesis, characterized by fatigue, which is exacerbated after minimal exercise. We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signaling as an under-pinning of the fatigue state. A carefully-characterized sample of patients with CFS (N = 10) and healthy matched control participants (N = 12) were included. Participant ratings of fatigue and other symptoms, as well as blood samples, were obtained at baseline, and five other time-points up to 72 h after 25 min of moderate-intensity cycling exercise...
2016: Frontiers in Physiology
Christopher J Davis, Ping Taishi, Kimberly A Honn, John N Koberstein, James M Krueger
The ionotropic purine type 2X7 receptor (P2X7R) is a non-specific cation channel implicated in sleep regulation and brain cytokine release. Many endogenous rhythms co-vary with sleep including locomotor activity and core body temperature. Further, brain-hypothalamic cytokines and purines play a role in the regulation of these physiological parameters as well as sleep. We hypothesized that these parameters are also affected by the absence of the P2X7 receptor. Herein we determine spontaneous expression of body temperature and locomotor activity in WT and P2X7R knockout (KO) mice and how they are affected by sleep deprivation (SD)...
October 5, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Silke Agte, Thomas Pannicke, Elke Ulbricht, Andreas Reichenbach, Andreas Bringmann
Tractional forces or mechanical stimulation are known to induce calcium responses in retinal glial cells. The aim of the study was to determine the characteristics of calcium responses in Müller glial cells of the avascular guinea pig retina induced by focal mechanical stimulation. Freshly isolated retinal wholemounts were loaded with Mitotracker Deep Red (to fill Müller cells) and the calcium-sensitive dye Fluo-4/AM. The inner retinal surface was mechanically stimulated with a micropipette tip for 10 ms...
October 5, 2016: Glia
Lihua Ma, Thu Trinh, Yanfang Ren, Robert T Dirksen, Xiuxin Liu
ATP induces pain via activation of purinergic receptors in nociceptive sensory nerves. ATP signaling is terminated by ATP hydrolysis mediated by cell surface-localized ecto-nucleotidases. Using enzymatic histochemical staining, we show that ecto-ATPase activity is present in mouse trigeminal nerves. Using immunofluorescence staining, we found that ecto-NTPDase3 is expressed in trigeminal nociceptive neurons and their projections to the brainstem. In addition, ecto-ATPase activity and ecto-NTPDase3 are also detected in the nociceptive outermost layer of the trigeminal subnucleus caudalis...
2016: PloS One
Laura Korvers, Amanda de Andrade Costa, Martin Mersch, Vitali Matyash, Helmut Kettenmann, Marcus Semtner
Microglia are the resident immune cells in the central nervous system and many of their physiological functions are known to be linked to intracellular calcium (Ca(2+)) signaling. Here we show that isolated and purified mouse microglia-either freshly or cultured-display spontaneous and transient Ca(2+) elevations lasting for around ten to twenty seconds and occurring at frequencies of around five to ten events per hour and cell. The events were absent after depletion of internal Ca(2+) stores, by phospholipase C (PLC) inhibition or blockade of inositol-1,4,5-trisphosphate receptors (IP3Rs), but not by removal of extracellular Ca(2+), indicating that Ca(2+) is released from endoplasmic reticulum intracellular stores...
September 22, 2016: Cell Calcium
Roberto M Maciel, Fabiano B Carvalho, Ayodeji A Olabiyi, Roberta Schmatz, Jessié M Gutierres, Naiara Stefanello, Daniela Zanini, Michelle M Rosa, Cinthia M Andrade, Maribel A Rubin, Maria Rosa Schetinger, Vera Maria Morsch, Cristiane C Danesi, Sonia T A Lopes
The present study investigated the protective effect of quercetin (Querc) on memory, anxiety-like behavior and impairment of ectonucleotidases and acetylcholinesterase (AChE) activities in brain of streptozotocin-induced diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and administered by gavage at the doses of 5, 25 and 50mg/kg once a day during 40days...
September 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hiroki Koizumi, Shoji Ikezaki, Toyoaki Ohbuchi, Ba Hung Do, Nobusuke Hohchi, Rintaro Kawaguchi, Takuro Kitamura, Hideaki Suzuki
OBJECTIVE: The present study aimed at investigating ATP release in response to acetylcholine (Ach) and pharmacologically elucidating the intracellular signal transduction pathway of this reaction in an ex vivo experiment. METHODS: The inferior turbinate mucosa was collected from 21 patients with chronic hypertrophic rhinitis who underwent endoscopic turbinectomy. The mucosa was shaped into a filmy round piece, and incubated with chemical(s) in Hank's balanced salt solution for 10min...
September 27, 2016: Auris, Nasus, Larynx
Yutaka Shishikura, Akira Koarai, Hiroyuki Aizawa, Mutsuo Yamaya, Hisatoshi Sugiura, Mika Watanabe, Yuichiro Hashimoto, Tadahisa Numakura, Tomonori Makiguti, Kyoko Abe, Mituhiro Yamada, Toshiaki Kikuchi, Yasushi Hoshikawa, Yoshinori Okada, Masakazu Ichinose
BACKGROUND: In response to tissue damage or inflammation, adenosine-5'-triphosphate (ATP) is released into the extracellular compartment and has been demonstrated to augment inflammation via purinergic P2 receptors (P2Rs). Recently, ATP has been shown to be increased in the airways of COPD patients. In the present study, we examined the possible involvement of extracellular ATP in airway mucus hypersecretion during viral-induced COPD exacerbations. METHODS: The involvement of extracellular ATP in the release of a major airway mucin, MUC5AC, and its signal pathway was examined after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of dsRNA to mimic viral infection, and rhinovirus (RV) infection in NCI-H292 cells and differentiated airway epithelial cells from COPD patients...
September 27, 2016: Respiratory Research
Mélissa Bol, Nan Wang, Marijke De Bock, Benjamin Wacquier, Elke Decrock, Ashish Gadicherla, Kelly Decaluwé, Bert Vanheel, Harold V van Rijen, Dmitri V Krysko, Geert Bultynck, Geneviève Dupont, Johan Van de Voorde, Luc Leybaert
AIMS: Connexins form gap-junctions (GJs) that directly connect cells, thereby coordinating vascular cell function and controlling vessel diameter and blood flow. GJs are composed of two hemichannels contributed by each of the connecting cells. Hemichannels also exist as non-junctional channels that, when open, lead to the entry/loss of ions and the escape of ATP. Here we investigated cross-talk between hemichannels and Ca(2+)/purinergic signaling in controlling blood vessel contraction...
September 27, 2016: Cardiovascular Research
Qian Gao, Hanxiao Ren, Mingkun Chen, Ziguang Niu, Haibo Tao, Yin Jia, Jianrong Zhang, Wenjie Li
β-crystallin B2 (CRYBB2) knockout mice exhibit morphological and functional abnormalities in the ovary. Long non‑coding RNAs (lncRNAs) regulate gene transcription and translation, and epigenetic modification of genomic DNA. The present study investigated the role of lncRNAs in mediating the effects of CRYBB2 in the regulation of ovary development in mice. In the current study, ovary tissues from wild‑type (WT) and CRYBB2 knockout mice were subjected to lncRNA and mRNA microarray profiling. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to group the differentially expressed lncRNAs into regulated gene pathways and functions...
September 22, 2016: Molecular Medicine Reports
K Barth, R Bläsche, A Neißer, S Bramke, J A Frank, M Kasper
The purinergic receptor P2X7 represents an ATP-gated ionotropic receptor with a selective localization in alveolar epithelial type I cells of the lung. Despite the involvement of the receptor in inflammatory processes of the lung, it is not established whether this receptor plays a specific role in the alveolar epithelial cell biology. There is evidence that P2X7 receptor influences Wnt/β-catenin signalling pathways in alveolar epithelial cells under conditions of injury. Here, we investigated the expression of GSK-3β, a potent protein kinase involved in alveolar epithelial barrier functions, and of tight junction molecules occludin, claudin-4 and claudin-18 in wild-type and P2X7(-/-) mice...
September 23, 2016: Histochemistry and Cell Biology
Geoffrey Burnstock
The roles of purinergic signalling in diseases of the central nervous system and the potential use of purinergic compounds for their treatment are attracting increasing attention. In this review, the focus is on the findings reported in recent papers and reviews to update knowledge in this field.
September 22, 2016: CNS & Neurological Disorders Drug Targets
Ramasri Sathanoori, Paulina Bryl-Gorecka, Christa E Müller, Laurie Erb, Gary A Weisman, Björn Olde, David Erlinge
Endothelial cells release ATP in response to fluid shear stress, which activates purinergic (P2) receptor-mediated signaling molecules including endothelial nitric oxide (eNOS), a regulator of vascular tone. While P2 receptor-mediated signaling in the vasculature is well studied, the role of P2Y2 receptors in shear stress-associated endothelial cell alignment, cytoskeletal alterations, and wound repair remains ill defined. To address these aspects, human umbilical vein endothelial cell (HUVEC) monolayers were cultured on gelatin-coated dishes and subjected to a shear stress of 1 Pa...
September 20, 2016: Cellular and Molecular Life Sciences: CMLS
Martin S Minns, Vickery Trinkaus-Randall
Nucleotide release and purinergic signaling make up the earliest response to corneal injury and are vital for proper wound healing. In this study, we review the importance of nucleotide release in the injury response and focus on the contribution of 2 receptors that mediate purinergic signaling, P2Y2 and P2X7. These receptors mediate the early response to injury and activate downstream signaling to promote cytoskeletal rearrangement and cell migration. The contribution of corneal nerves to the purinergic injury response is also discussed...
September 19, 2016: Journal of Ocular Pharmacology and Therapeutics
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