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Purinergic Signalling

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https://www.readbyqxmd.com/read/28409324/generation-and-characterization-of-polyclonal-and-monoclonal-antibodies-to-human-ntpdase2-including-a-blocking-antibody
#1
Julie Pelletier, Hervé Agonsanou, Ninotchska Delvalle, Michel Fausther, Mabrouka Salem, Brian Gulbransen, Jean Sévigny
Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) is an ectonucleotidase that modulates P2 receptor activation by hydrolyzing ATP to ADP. In rodents, NTPDase2 is expressed by several specialized cell types such as vascular adventitial cells, neuroglial cells, hepatic portal fibroblasts, gustatory type I cells, and cells within the connective tissues of reproductive and gastrointestinal organs. Much less is known regarding the expression and function of NTPDase2 in humans. Here, we developed specific research tools to study human NTPDase2...
April 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28397110/potential-role-of-p2x7r-in-esophageal-squamous-cell-carcinoma-proliferation
#2
André A Santos, Angélica R Cappellari, Fernanda O de Marchi, Marina P Gehring, Aline Zaparte, Caroline A Brandão, Tiago Giuliani Lopes, Vinicius D da Silva, Luis Felipe Ribeiro Pinto, Luiz Eduardo Baggio Savio, Aline Cristina Abreu Moreira-Souza, Robson Coutinho-Silva, Juliano D Paccez, Luiz F Zerbini, Fernanda B Morrone
Esophageal cancer is an aggressive tumor and is the sixth leading cause of cancer death worldwide. ATP is well known to regulate cancer progression in a variety of models by different mechanisms, including P2X7R activation. This study aimed to evaluate the role of P2X7R in esophageal squamous cell carcinoma (ESCC) proliferation. Our results show that treatment with high ATP concentrations induced a decrease in cell number, cell viability, number of polyclonal colonies, and reduced migration of ESCC. The treatment with the selective P2X7R antagonist A740003 or siRNA for P2X7 reverted this effect in the KYSE450 cell line...
April 11, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28353082/erratum-to-the-effect-of-sinomenine-in-diabetic-neuropathic-pain-mediated-by-the-p2x3-receptor-in-dorsal-root-ganglia
#3
Shenqiang Rao, Shuangmei Liu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Bing Wu, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Changshui Xu, Guilin Li, Hong Xu, Chunping Zhang, Shangdong Liang
No abstract text is available yet for this article.
March 28, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28343356/development-of-a-novel-strategy-to-target-cd39-antithrombotic-activity-to-the-endothelial-platelet-microenvironment-in-kidney-ischemia-reperfusion-injury
#4
Maithili Sashindranath, Karen M Dwyer, Shala Dezfouli, Carly Selan, Sandra Crikis, Bo Lu, Yuping Yuan, Michael J Hickey, Karlheinz Peter, Simon C Robson, Peter J Cowan, Harshal H Nandurkar
Kidney ischemia-reperfusion injury (IRI) is common during transplantation. IRI is characterised by inflammation and thrombosis and associated with acute and chronic graft dysfunction. P-selectin and its ligand PSGL-1 are cell adhesion molecules that control leukocyte-endothelial and leukocyte-platelet interactions under inflammatory conditions. CD39 is the dominant vascular nucleotidase that facilitates adenosine generation via extracellular ATP/ADP-phosphohydrolysis. Adenosine signalling is protective in renal IRI, but CD39 catalytic activity is lost with exposure to oxidant stress...
March 25, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28285440/plasmodium-falciparum-gfp-e-ntpdase-expression-at-the-intraerythrocytic-stages-and-its-inhibition-blocks-the-development-of-the-human-malaria-parasite
#5
Lucas Borges-Pereira, Kamila Anna Meissner, Carsten Wrenger, Célia R S Garcia
Plasmodium falciparum is the causative agent of the most dangerous form of malaria in humans. It has been reported that the P. falciparum genome encodes for a single ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), an enzyme that hydrolyzes extracellular tri- and di-phosphate nucleotides. The E-NTPDases are known for participating in invasion and as a virulence factor in many pathogenic protozoa. Despite its presence in the parasite genome, currently, no information exists about the activity of this predicted protein...
March 11, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28233082/prasugrel-suppresses-development-of-lithium-induced-nephrogenic-diabetes-insipidus-in-mice
#6
Yue Zhang, János Peti-Peterdi, Anna U Brandes, Anne Riquier-Brison, Noel G Carlson, Christa E Müller, Carolyn M Ecelbarger, Bellamkonda K Kishore
Previously, we localized ADP-activated P2Y12 receptor (R) in rodent kidney and showed that its blockade by clopidogrel bisulfate (CLPD) attenuates lithium (Li)-induced nephrogenic diabetes insipidus (NDI). Here, we evaluated the effect of prasugrel (PRSG) administration on Li-induced NDI in mice. Both CLPD and PRSG belong to the thienopyridine class of ADP receptor antagonists. Groups of age-matched adult male B6D2 mice (N = 5/group) were fed either regular rodent chow (CNT), or with added LiCl (40 mmol/kg chow) or PRSG in drinking water (10 mg/kg bw/day) or a combination of LiCl and PRSG for 14 days and then euthanized...
February 23, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28176024/hyperosmotic-stress-induces-atp-release-and-changes-in-p2x7-receptor-levels-in-human-corneal-and-conjunctival-epithelial-cells
#7
Ana Guzman-Aranguez, María J Pérez de Lara, Jesús Pintor
Tear hyperosmolarity is a key event in dry eye. In this work, we analyzed whether hyperosmolar challenge induces ATP release on the ocular surface. Moreover, as extracellular ATP can activate P2X7 receptor, the changes in P2X7 protein levels and its involvement in pathological process triggered by hypertonic treatment were also examined. High-performance liquid chromatography analysis revealed that ATP levels significantly increased in human corneal and conjunctival epithelial cells exposed to hyperosmotic challenge as well as in dry eye patients as compared to control subjects...
February 7, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28025718/conformational-changes-during-human-p2x7-receptor-activation-examined-by-structural-modelling-and-cysteine-based-cross-linking-studies
#8
Emily A Caseley, Stephen P Muench, Lin-Hua Jiang
The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27900516/nucleotides-and-nucleoside-signaling-in-the-regulation-of-the-epithelium-to-mesenchymal-transition-emt
#9
REVIEW
A S Martínez-Ramírez, M Díaz-Muñoz, A Butanda-Ochoa, F G Vázquez-Cuevas
The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27832456/regulation-of-cd73-in-the-development-of-lower-limb-atherosclerosis
#10
Juho Jalkanen, Maija Hollmén, Sirpa Jalkanen, Harri Hakovirta
Atherosclerosis is an inflammatory process of the arterial wall. CD73 (also known as ecto-5'-nucleotidase) is a key regulator of cell signaling in response to inflammation and hypoxia, and may be important in the development of atherosclerosis. Recently, we have shown that high CD73 activity can be detected in the serum of patients with peripheral arterial disease (PAD). Using this same PAD patient cohort of 226 subjects with 38 femoral artery samples obtained during surgical endarcterectomy and control artery samples taken during autopsy, we explored the association of serum CD73 activity with overall atherosclerotic burden and the expression of CD73 in mature and developing plaques...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27817132/inhibitory-effect-of-estrogen-receptor-beta-on-p2x3-receptors-during-inflammation-in-rats
#11
Qian Jiang, Wen-Xin Li, Jia-Run Sun, Tian-Tian Zhu, Juan Fan, Li-Hua Yu, Geoffrey Burnstock, Hua Yang, Bei Ma
Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27815804/lung-injury-during-lps-induced-inflammation-occurs-independently-of-the-receptor-p2y1
#12
Elisabetta Liverani
Disruption of the lung endothelial and epithelial barriers during acute inflammation leads to excessive neutrophil migration. It is likely that activated platelets promote pulmonary recruitment of neutrophils during inflammation, and previous studies have found that anti-platelet therapy and depletion of circulating platelets have lung-protective effects in different models of inflammation. Because ADP signaling is important for platelet activation, I investigated the role of the ADP-receptor P2Y1, a G protein-coupled receptor expressed on the surface of circulating platelets, during lipopolysaccharide (LPS)-induced inflammation and lung injury in P2Y1-null and wild-type mice...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27766552/synthesis-characterization-and-in-vitro-evaluation-of-the-selective-p2y2-receptor-antagonist-ar-c118925
#13
Muhammad Rafehi, Joachim C Burbiel, Isaac Y Attah, Aliaa Abdelrahman, Christa E Müller
The Gq protein-coupled, ATP- and UTP-activated P2Y2 receptor is a potential drug target for a range of different disorders, including tumor metastasis, inflammation, atherosclerosis, kidney disorders, and osteoporosis, but pharmacological studies are impeded by the limited availability of suitable antagonists. One of the most potent and selective antagonists is the thiouracil derivative AR-C118925. However, this compound was until recently not commercially available and little is known about its properties...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27761681/diadenosine-tetraphosphate-ap4a-inhibits-atp-induced-excitotoxicity-a-neuroprotective-strategy-for-traumatic-spinal-cord-injury-treatment
#14
David Reigada, Rosa María Navarro-Ruiz, Marcos Javier Caballero-López, Ángela Del Águila, Teresa Muñoz-Galdeano, Rodrigo M Maza, Manuel Nieto-Díaz
Reducing cell death during the secondary injury is a major priority in the development of a cure for traumatic spinal cord injury (SCI). One of the earliest processes that follow SCI is the excitotoxicity resulting from the massive release of excitotoxicity mediators, including ATP, which induce an excessive and/or prolonged activation of their receptors and a deregulation of the calcium homeostasis. Diadenosine tetraphosphate (Ap4A) is an endogenous purinergic agonist, present in both extracellular and intracellular fluids, with promising cytoprotective effects in different diseases including neurodegenerative processes...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27757785/2-3-o-substituted-atp-derivatives-as-potent-antagonists-of-purinergic-p2x3-receptors-and-potential-analgesic-agents
#15
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27696086/adenosine-a2a-receptor-regulates-expression-of-vascular-endothelial-growth-factor-in-feto-placental-endothelium-from-normal-and-late-onset-pre-eclamptic-pregnancies
#16
Jesenia Acurio, Kurt Herlitz, Felipe Troncoso, Claudio Aguayo, Patricio Bertoglia, Carlos Escudero
We aim to investigate whether A2A/nitric oxide-mediated regulation of vascular endothelial growth factor (VEGF) expression is impaired in feto-placental endothelial cells from late-onset pre-eclampsia. Cultures of human umbilical vein endothelial cells (HUVECs) and human placental microvascular endothelial cells (hPMECs) from normal and pre-eclamptic pregnancies were used. Assays by using small interference RNA (siRNA) for A2A were performed, and transfected cells were used for estimation of messenger RNA (mRNA) levels of VEGF, as well as for cell proliferation and angiogenesis in vitro...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27696085/transcriptomic-effects-of-adenosine-2a-receptor-deletion-in-healthy-and-endotoxemic-murine-myocardium
#17
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/27683228/microvesicles-shed-from-microglia-activated-by-the-p2x7-p38-pathway-are-involved-in-neuropathic-pain-induced-by-spinal-nerve-ligation-in-rats
#18
Jian Li, Xiangnan Li, Xin Jiang, Mei Yang, Rui Yang, Geoffrey Burnstock, Zhenghua Xiang, Hongbin Yuan
Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β...
March 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28054206/the-effect-of-sinomenine-in-diabetic-neuropathic-pain-mediated-by-the-p2x3-receptor-in-dorsal-root-ganglia
#19
Shenqiang Rao, Shuangmei Liu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Bing Wu, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Changshui Xu, Guilin Li, Hong Xu, Chunping Zhang, Shangdong Liang
Type 2 diabetes mellitus (T2DM) accounts for more than 90% of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. Sinomenine is a natural bioactive component extracted from the Sinomenium acutum and has anti-inflammatory effects. The aim of our study was to investigate the effects of sinomenine on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower than those of control rats...
January 4, 2017: Purinergic Signalling
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
#20
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
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