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https://www.readbyqxmd.com/read/29149731/purinergic-drug-targets-for-gastrointestinal-disorders
#1
REVIEW
Geoffrey Burnstock, Kenneth A Jacobson, Fievos L Christofi
Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuronal, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuron death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway...
November 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29146440/clodronate-a-vesicular-atp-release-blocker
#2
REVIEW
Yoshinori Moriyama, Masatoshi Nomura
Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VNUT), a transporter responsible for vesicular storage of ATP. Clodronate inhibits vesicular ATP release from neurons and reduces chronic neuropathic and inflammatory pain following blockade of purinergic chemical transmission...
November 13, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29143994/intermittent-compressive-force-induces-human-mandibular-derived-osteoblast-differentiation-via-wnt-%C3%AE-catenin-signaling
#3
Pimrumpai Rochanakit Sindhavajiva, Panunn Sastravaha, Mansuang Arksornnukit, Prasit Pavasant
Mechanical force induces an efflux of ATP that regulates osteoblast differentiation. However, the effect of mechanical force-induced ATP efflux on WNT/β-catenin signaling remains unclarified. The aim of this study was to investigate the effect of intermittent compressive force (ICF) and ICF-induced extracellular ATP on osteoblast differentiation via WNT/β-catenin signaling in human mandibular-derived osteoblast precursors (hMOBPs). The hMOBPs were subjected to ICF (1.5 g/cm(2) , 0.3 Hz) for 20 h. To investigate the role of ATP, Apyrase (0...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29138822/fucoidan-inhibits-ca2-responses-induced-by-a-wide-spectrum-of-agonists-for-g%C3%A2-protein%C3%A2-coupled-receptors
#4
Hong Wu, Shuibo Gao, Min Fu, Takashi Sakurai, Susumu Terakawa
Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been used in traditional Chinese herbal medicine to treat thyroid tumors for many years. Although a number of its cellular effects have been investigated, the role of fucoidan in molecular signaling, particularly in Ca2+ signaling, remains largely unknown. In the present study, the effects of fucoidan on Ca2+ responses in HeLa cells, human umbilical vein endothelial cells and astrocytes were investigated using a wide range of receptor agonists...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29136654/vascular-surgical-stretch-injury-leads-to-activation-of-p2x7-receptors-and-impaired-endothelial-function
#5
Padmini Komalavilas, Weifeng Luo, Christy M Guth, Olukemi Jolayemi, Rachel I Bartelson, Joyce Cheung-Flynn, Colleen M Brophy
A viable vascular endothelial layer prevents vasomotor dysfunction, thrombosis, inflammation, and intimal hyperplasia. Injury to the endothelium occurs during harvest and "back table" preparation of human saphenous vein prior to implantation as an arterial bypass conduit. A subfailure overstretch model of rat aorta was used to show that subfailure stretch injury of vascular tissue leads to impaired endothelial-dependent relaxation. Stretch-induced impaired relaxation was mitigated by treatment with purinergic P2X7 receptor (P2X7R) inhibitors, brilliant blue FCF (FCF) and A740003, or apyrase, an enzyme that catalyzes the hydrolysis of ATP...
2017: PloS One
https://www.readbyqxmd.com/read/29134411/distinct-roles-of-ecto-nucleoside-triphosphate-diphosphohydrolase-2-ntpdase2-in-liver-regeneration-and-fibrosis
#6
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/29127888/histamine-stimulates-secretion-of-extracellular-vesicles-with-nucleotidase-activity-in-rat-submandibular-gland
#7
Débora Alejandra González, Martín Matías Barbieri van Haaster, Emmanuel Quinteros Villarruel, Macarena Brandt, María Belén Benítez, Graciela Mabel Stranieri, Betina Orman
BACKGROUND: Extracellular vesicles released by different cells have been isolated from diverse fluids including saliva. We previously reported that rat submandibular glands secrete nanovesicles that catalyze hydrolysis of ATP, ADP and AMP, which are actors of the purinergic signaling system along with adenosine. Extracellular nucleotides like ATP and adenosine are involved in the regulation of inflammatory processes and apoptosis. Histamine, a widely distributed biogenic amine, is involved in inflammatory response...
October 18, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29127599/cb1-receptors-mediated-inhibition-of-atp-induced-ca-2-i-increase-in-cultured-rat-spinal-dorsal-horn-neurons
#8
Jingdong Long, Xiaolu Lei, Meiyun Chen, Shulei Yang, Tao Sun, Junwei Zeng, Deqian Yu, Hong Tian, Xiaohong Liu
Spinal cannabinoid receptor 1 (CB1R) and purinergic P2X receptors (P2XR) play a critical role in the process of pathological pain. Both CB1R and P2XR are expressed in spinal dorsal horn (DH) neurons. It is not clear whether CB1 receptor activation modulates the function of P2X receptor channels within dorsal horn. For this reason, we observed the effect of CP55940 (cannabinoid receptor agonist) on ATP-induced Ca(2+) mobilization in cultured rat DH neurons. The changes of intracellular calcium concentration ([Ca(2+)]i) were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator...
November 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29126223/atheroprone-flow-activates-inflammation-via-endothelial-atp-dependent-p2x7-p38-signalling
#9
Jack P Green, Celine Souilhol, Ioannis Xanthis, Laura Martinez-Campesino, Neil P Bowden, Paul C Evans, Heather L Wilson
Objective: Atherosclerosis is a focal disease occurring at arterial sites of disturbed blood flow that generates low oscillating shear stress. Endothelial inflammatory signalling is enhanced at sites of disturbed flow via mechanisms that are incompletely understood. The influence of disturbed flow on endothelial ATP receptors and downstream signalling was assessed. Methods and Results: Cultured human endothelial cells were exposed to atheroprotective (high uniform) or atheroprone (low oscillatory) shear stress for 72 hours prior to assessment of ATP responses...
November 6, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29124970/a-review-on-the-nucleic-acid-constituents-in-mushrooms-nucleobases-nucleosides-and-nucleotides
#10
Chia-Wei Phan, Joon-Keong Wang, Shiau-Chuen Cheah, Murali Naidu, Pamela David, Vikineswary Sabaratnam
Mushrooms have become increasingly important as a reliable food source. They have also been recognized as an important source of bioactive compounds of high nutritional and medicinal values. The nucleobases, nucleosides and nucleotides found in mushrooms play important roles in the regulation of various physiological processes in the human body via the purinergic and/or pyrimidine receptors. Cordycepin, a 3'-deoxyadenosine found in Cordyceps sinensis has received much attention as it possesses many medicinal values including anticancer properties...
November 10, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/29122639/the-p2rx7-polymorphism-rs2230912-is-associated-with-depression-a-meta-analysis
#11
D Czamara, B Müller-Myhsok, S Lucae
Various studies have investigated whether single nucleotide polymorphisms (SNPs) in the gene purinergic receptor P2X7 (P2RX7), and rs2230912 specifically, were associated with mood disorders. While some studies found positive evidence, a large number of studies reported no significant associations. In a previously published meta-analysis, Feng et al. did not find a significant association and only moderate odds ratios (ORs) in case-control studies. They reported significant findings only for family-based studies...
November 6, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29121644/imaging-extracellular-atp-with-a-genetically-encoded-ratiometric-fluorescent-sensor
#12
Jason M Conley, Saranya Radhakrishnan, Stephen A Valentino, Mathew Tantama
Extracellular adenosine triphosphate (ATP) is a key purinergic signal that mediates cell-to-cell communication both within and between organ systems. We address the need for a robust and minimally invasive approach to measuring extracellular ATP by re-engineering the ATeam ATP sensor to be expressed on the cell surface. Using this approach, we image real-time changes in extracellular ATP levels with a sensor that is fully genetically-encoded and does not require an exogenous substrate. In addition, the sensor is ratiometric to allow for reliable quantitation of extracellular ATP fluxes...
2017: PloS One
https://www.readbyqxmd.com/read/29120881/atp-and-t-cell-mediated-rejection
#13
Eduardo Castillo-Leon, Sergio Dellepiane, Paolo Fiorina
PURPOSE OF REVIEW: Purine nucleosides and nucleotides are released in the extracellular space following cell injury and act as paracrine mediators through a number of dedicated membrane receptors. In particular, extracellular ATP (eATP) significantly influences T-lymphocyte activation and phenotype. The purpose of this review is to discuss the role of ATP signaling in the T-cell-mediated alloimmune response. RECENT FINDINGS: In various animal models of solid transplantation, the purinergic axis has been targeted to prevent acute rejection and to promote long-term graft tolerance...
November 7, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29115642/combined-treatment-with-extracorporeal-shock%C3%A2-wave-therapy-and-bone-marrow-mesenchymal-stem-cell-transplantation-improves-bone-repair-in-a-rabbit-model-of-bone-nonunion
#14
Tao Fan, Guozhi Huang, Wen Wu, Rong Guo, Qing Zeng
The aim of the present study was to analyze whether extracorporeal shock‑wave therapy (ESWT) combined with bone marrow mesenchymal stem cell (BMMSC) transplantation improves bone repair in a rabbit bone nonunion model. ESWT combined with BMMSC effectively enhanced mechanical strength, fracture stiffness and histological scores, and increased alkaline phosphatase activity, and osteopontin, runt related transcription factor 2 and collagen type I α1 chain protein expression levels in a rabbit bone nonunion model...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111328/3-naphthalen-2-yl-propoxy-methyl-azetidine-hydrochloride-attenuates-nlrp3-inflammasome-mediated-signaling-pathway-in-lipopolysaccharide-stimulated-bv2-microglial-cells
#15
Ji Woong Yang, Seung-Ju Yang, Jung-Min Na, Hoh-Gyu Hahn, Sung-Woo Cho
The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome is a multiprotein complex with a role in innate immune responses. NLRP3 inflammasome dysfunction is a common feature of chronic inflammatory diseases. Microglia activation is also associated with neuroinflammatory pathologies. We previously reported that 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) reduced hypoxia-induced toxicity by modulating inflammation. However, no studies have elucidated the precise mechanisms for the anti-inflammatory action of KHG26792, in particular via inflammasome mediation...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29110801/enhanced-electrical-field-stimulated-nitrergic-and-purinergic-vasoreactivity-in-distal-vs-proximal-internal-pudendal-arteries
#16
Michael R Odom, Elena S Pak, David A Brown, Johanna L Hannan
BACKGROUND: The internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and chronic kidney disease, thus contributing to erectile dysfunction. Interestingly, vascular remodeling primarily occurs in the distal and not in the proximal IPA, suggesting distinct local physiologic signaling differences within the IPA. AIM: To examine the role of purinergic signaling and neurotransmitter release by electrical field stimulation (EFS) in the regulation of proximal and distal IPA vascular tone...
November 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29103803/cd39-and-cd73-activity-are-protective-in-a-mouse-model-of-antiphospholipid-antibody-induced-miscarriages
#17
Anushka N Samudra, Karen M Dwyer, Carly Selan, Susanna Freddi, Lisa Murray-Segal, Mandana Nikpour, Michael J Hickey, Karlheinz Peter, Simon C Robson, Maithili Sashindranath, Peter J Cowan, Harshal H Nandurkar
OBJECTIVE: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder of young adults associated with devastating pregnancy complications (recurrent miscarriages, preeclampsia and low birth weight) and vascular complications including thrombosis. The key components implicated in pathogenesis of APS are the complement cascade and tissue factor (TF) activity causing inflammation and coagulation. Purinergic signalling involving catabolism of ATP to adenosine by cell-surface enzymes CD39 and CD73 has anti-inflammatory and anti-thrombotic effects...
November 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29092813/cell-membrane-disruption-stimulates-camp-and-ca-2-signaling-to-potentiate-cell-membrane-resealing-in-neighboring-cells
#18
Tatsuru Togo
Disruption of cellular plasma membranes, a common event in many animal tissues, is usually rapidly resealed. Moreover, repeated membrane disruptions within a single cell reseal faster than the initial wound in a protein kinase A (PKA) and protein kinase C (PKC)-dependent manner. In addition to wounded cells, recent studies have demonstrated that wounding of Madin-Darby canine kidney (MDCK) cells potentiates membrane resealing in neighboring cells in the short-term by purinergic signaling and in the long-term by nitric oxide/protein kinase G signaling...
November 1, 2017: Biology Open
https://www.readbyqxmd.com/read/29090621/post-thyroidectomy-hypothyroidism-increases-the-expression-and-activity-of-ectonucleotidases-in-platelets-possible-involvement-of-reactive-oxygen-species
#19
Jucimara Baldissarelli, Micheli M Pillat, Roberta Schmatz, Andréia M Cardoso, Fátima H Abdalla, Juliana S de Oliveira, Carla R N Polachini, Emerson Casali, Clarissa Pereira Bornemann, Henning Ulrich, Vera M Morsch, Maria R C Schetinger
Signaling mediated by purines is a widespread mechanism of cell-cell communication related to vasomotor responses and the control of platelet function in the vascular system. However, little is known about the involvement of this signaling as well as the role of reactive oxygen species (ROS) in the development of hypothyroidism. Therefore, the present study investigates changes in the purinergic system, including enzyme activities and expression in platelets, and oxidative profiles in patients with post-thyroidectomy hypothyroidism...
November 1, 2017: Platelets
https://www.readbyqxmd.com/read/29079688/heterozygosity-for-the-mood-disorder-associated-variant-gln460arg-alters-p2x7-receptor-function-and-sleep-quality
#20
Michael W Metzger, Sandra M Walser, Nina Dedic, Fernando Aprile-Garcia, Vladimira Jakubcakova, Marek Adamczyk, Katharine J Webb, Manfred Uhr, Damian Refojo, Mathias V Schmidt, Elisabeth Friess, Axel Steiger, Mayumi Kimura, Alon Chen, Florian Holsboer, Eduardo Arzt, Wolfgang Wurst, Jan M Deussing
A single-nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice co-expressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation...
October 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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