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Purinergic signalling

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https://www.readbyqxmd.com/read/28344879/prostaglandin-e2-mediated-adenosinergic-effects-on-cd14-cells-self-amplifying-immunosuppression-in-cancer
#1
Saly Al-Taei, Josephine Salimu, Lisa K Spary, Aled Clayton, Jason F Lester, Zsuzsanna Tabi
CD39 and CD73 are surface-expressed ectonucleotidases that hydrolyze ATP in a highly regulated, serial manner into ADP, AMP and adenosine. The end product, adenosine, has both tumor-promoting and immunosuppressive effects. The aim of this study was to determine CD73 expression on immune cells in pleural effusion (PE) in order to have a better understanding of the immune environment in mesothelioma. PE- or blood-derived CD14(+) cells of mesothelioma patients and healthy donors were analyzed by flow cytometry for the expression of CD39 and CD73...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28339693/neuronal-signaling-repertoire-in-the-mammalian-sperm-functionality
#2
Alfredo Ramírez-Reveco, Franz Villarroel-Espíndola, Joan E Rodríguez-Gil, Ilona I Concha
The common embryonic origin has been a recurrent explanation to understand the presence of "neural receptors" in sperm. However, this designation has conditioned a bias marked by the classical neurotransmission model, dismissing the possibility that neurotransmitters can play specific roles in the sperm function by themselves. For instance, the launching of acrosome reaction, a fundamental sperm function, includes several steps that recall the process of presynaptic secretion. Unlike of postsynaptic neuron, whose activation is mediated by molecular interaction between neurotransmitter and postsynaptic receptors, the oocyte activation is not mediated by receptors, but by cytosolic translocation of sperm phospholipase (PLCζ)...
February 20, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28318884/udp-p2y6-receptor-signaling-regulates-ige-dependent-degranulation-in-human-basophils
#3
Manabu Nakano, Koichi Ito, Takeo Yuno, Nobuyuki Soma, Syun Aburakawa, Kosuke Kasai, Toshiya Nakamura, Hideki Takami
BACKGROUND: P2Y purinergic receptors (P2YR) are G protein-coupled receptors that are stimulated by extracellular nucleotides. They mediate cellular effects by regulating cAMP production, protein kinase C activation, inositol trisphosphate generation, and Ca(2+) release from intracellular stores. The P2Y6 receptor of this family is selectively stimulated by UDP, and selectively inhibited by MRS2578. In the present study, we examined the effect of UDP/P2Y6 receptor signaling on IgE-dependent degranulation in human basophils...
March 16, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28300322/astroglia-as-a-cellular-target-for-neuroprotection-and-treatment-of-neuro-psychiatric-disorders
#4
REVIEW
Beihui Liu, Anja G Teschemacher, Sergey Kasparov
Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem-cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability...
March 16, 2017: Glia
https://www.readbyqxmd.com/read/28300164/role-of-purinergic-signaling-in-experimental-pneumococcal-meningitis
#5
Marco Zierhut, Susanne Dyckhoff, Ilias Masouris, Matthias Klein, Sven Hammerschmidt, Hans-Walter Pfister, Korcan Ayata, Marco Idzko, Uwe Koedel
Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298636/the-purinergic-receptor-p2x5-regulates-inflammasome-activity-and-hyper-multinucleation-of-murine-osteoclasts
#6
Hyunsoo Kim, Matthew C Walsh, Noriko Takegahara, Sarah A Middleton, Hong-In Shin, Junhyong Kim, Yongwon Choi
Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss and hyper-multinucleation of OCs...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284836/exciting-and-not-so-exciting-roles-of-pannexins
#7
REVIEW
Eliana Scemes, Jana Velíšková
It is the current view that purinergic signaling regulates many physiological functions. Pannexin1 (Panx1), a member of the gap junction family of proteins is an ATP releasing channel that plays important physio-pathological roles in various tissues, including the CNS. Upon binding to purinergic receptors expressed in neural cells, ATP triggers cellular responses including increased cell proliferation, cell morphology changes, release of cytokines, and regulation of neuronal excitability via release of glutamate, GABA and ATP itself...
March 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28280061/purinergic-receptor-transactivation-by-the-%C3%AE-2-adrenergic-receptor-increases-intracellular-ca-2-in-non-excitable-cells
#8
Wayne Stallaert, Emma T van der Westhuizen, Anne-Marie Schonegge, Bianca Plouffe, Mireille Hogue, Viktoria Lukashova, Asuka Inoue, Satoru Ishida, Junken Aoki, Christian Le Gouill, Michel Bouvier
The β2 adrenergic receptor (β2AR) increases intracellular Ca(2+) in a variety of cell types. By combining pharmacological and genetic manipulations, we reveal a novel mechanism through which the β2AR promotes Ca(2+) mobilization (pEC50 = 7.32 ± 0.10) in non-excitable human embryonic kidney (HEK)-293S cells. Down-regulation of Gs with sustained cholera toxin pre-treatment and the use Gs-null HEK293 (ΔGs-HEK293) cells generated using the CRISPR/Cas9 system, combined with pharmacological modulation of cAMP formation revealed a Gs-dependent but cAMP-independent increase in intracellular Ca(2+) following β2AR stimulation...
March 9, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28280004/connexin-purinergic-signaling-in-enteric-glia-mediates-the-prolonged-effect-of-morphine-on-constipation
#9
Sukhada Bhave, Aravind Gade, Minho Kang, Kurt F Hauser, William L Dewey, Hamid I Akbarali
Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (in vivo) but not upon direct exposure of glia to morphine (in vitro)...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28265084/lys49-myotoxin-from-the-brazilian-lancehead-pit-viper-elicits-pain-through-regulated-atp-release
#10
Chuchu Zhang, Katalin F Medzihradszky, Elda E Sánchez, Allan I Basbaum, David Julius
Pain-producing animal venoms contain evolutionarily honed toxins that can be exploited to study and manipulate somatosensory and nociceptive signaling pathways. From a functional screen, we have identified a secreted phospholipase A2 (sPLA2)-like protein, BomoTx, from the Brazilian lancehead pit viper (Bothrops moojeni). BomoTx is closely related to a group of Lys49 myotoxins that have been shown to promote ATP release from myotubes through an unknown mechanism. Here we show that BomoTx excites a cohort of sensory neurons via ATP release and consequent activation of P2X2 and/or P2X3 purinergic receptors...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263802/abacavir-induces-platelet-endothelium-interactions-by-interfering-with-purinergic-signalling-a-step-from-inflammation-to-thrombosis
#11
Angeles Alvarez, Cesar Rios-Navarro, Maria Amparo Blanch-Ruiz, Victor Collado-Diaz, Isabel Andujar, Maria Angeles Martinez-Cuesta, Samuel Orden, Juan V Esplugues
The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway...
March 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28262230/placental-hemostasis-and-sterile-inflammation-new-insights-into-gestational-vascular-disease
#12
Shrey Kohli, Berend Isermann
Activation of the coagulation and inflammatory systems are physiologically occurring during pregnancy. However, excess activation of either system is well documented in gestational vascular diseases (GVD). GVD are placenta-mediated pregnancy complications and a major cause of feto-maternal morbidity and mortality. The causal relevance of excess coagulation and inflammatory responses for GVD remains largely unknown. Deciphering the causal relationship of excess coagulation and inflammation in GVD may allow conceptualizing new therapeutic approaches to combat GVD...
March 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28251649/evidence-for-purine-nucleoside-phosphorylase-pnp-release-from-rat-c6-glioma-cells
#13
Patricia Giuliani, Mariachiara Zuccarini, Silvana Buccella, Luis Emiliano Peña-Altamira, Elisabetta Polazzi, Marco Virgili, Barbara Monti, Alessandro Poli, Michel P Rathbone, Patrizia Di Iorio, Renata Ciccarelli, Francesco Caciagli
Intracellular purine turnover is mainly oriented to preserving the level of triphosphate nucleotides, fundamental molecules in vital cell functions that, when released outside cells, act as receptor signals. Conversely, high levels of purine bases and uric acid are found in the extracellular milieu, even in resting conditions. These compounds could derive from nucleosides/bases that, having escaped to cell reuptake, are metabolized by extracellular enzymes similar to the cytosolic ones. Focusing on purine nucleoside phosphorylase (PNP) that catalyzes the reversible phosphorolysis of purine (deoxy)-nucleosides/bases, we found that it is constitutively released from cultured rat C6 glioma cells into the medium, and has a molecular weight and enzyme activity similar to the cytosolic enzyme...
March 2, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28244110/the-p2x7-receptor-links-mechanical-strain-to-cytokine-il-6-upregulation-and-release-in-neurons-and-astrocytes
#14
Wennan Lu, Farraj Albalawi, Jonathan M Beckel, Jason C Lim, Alan M Laties, Claire H Mitchell
BACKGROUND: Mechanical strain in neural tissues can lead to the upregulation and release of multiple cytokines including IL-6. In the retina, the mechanosensitive release of ATP can autostimulate P2X7 receptors on both retinal ganglion cell neurons and optic nerve head astrocytes. Here we asked whether the purinergic signaling contributed to the IL-6 response to increased intraocular pressure (IOP) in vivo, and stretch or swelling in vitro. METHODS: Rat and mouse eyes were exposed to non-ischemic elevations in IOP to 50-60 mmHg for 4 hrs...
February 28, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28242818/characterization-of-flow-regulated-cortical-collecting-duct-endothelin-1-production
#15
Nirupama Ramkumar, Yang Gao, Donald E Kohan
Collecting duct (CD) endothelin-1 (ET-1) is an autocrine inhibitor of Na(+) and water reabsorption. Salt or water loading increases CD ET-1 production; this is likely due, at least in part, to increased tubule fluid flow. The mechanisms by which flow stimulates CD ET-1 production are incompletely understood. In particular, flow induction of cortical CD (CCD) and inner medullary CD (IMCD) ET-1 synthesis may occur via different mechanisms. Since flow-mediated ET-1 production in IMCD has been more extensively characterized than in the CCD, this study was undertaken to further examine putative signaling pathways involved in flow-stimulated CCD ET-1 production...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28239332/characterization-of-the-circumlimbal-suture-model-of-chronic-iop-elevation-in-mice-and-assessment-of-changes-in-gene-expression-of-stretch-sensitive-channels
#16
Da Zhao, Christine T O Nguyen, Vickie H Y Wong, Jeremiah K H Lim, Zheng He, Andrew I Jobling, Erica L Fletcher, Holly R Chinnery, Algis J Vingrys, Bang V Bui
To consider whether a circumlimbal suture can be used to chronically elevate intraocular pressure (IOP) in mice and to assess its effect on retinal structure, function and gene expression of stretch sensitive channels. Anesthetized adult C57BL6/J mice had a circumlimbal suture (10/0) applied around the equator of one eye. In treated eyes (n = 23) the suture was left in place for 12 weeks whilst in sham control eyes the suture was removed at day two (n = 17). Contralateral eyes served as untreated controls. IOP was measured after surgery and once a week thereafter...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28224484/introduction-to-the-special-issue-on-purinergic-receptors
#17
Geoffrey Burnstock
In this Introduction to the series of papers that follow about purinergic receptors, there is a brief history of the discovery of purinergic signalling, the identity of purinoceptors and the current recognition of P1, P2X and P2Y subtypes. An account of key functions mediated by purinoceptors follows, including examples of both short-term and long-term (trophic) signalling and a table showing the selective agonists and antagonists for the purinoceptor subtypes. References to evolution and roles of purinoceptors in pathological conditions are also presented...
February 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28223127/multidrug-resistance-in-glioblastoma-stem-like-cells-role-of-the-hypoxic-microenvironment-and-adenosine-signaling
#18
REVIEW
Daniel Uribe, Ángelo Torres, José Dellis Rocha, Ignacio Niechi, Carlos Oyarzún, Luis Sobrevia, Rody San Martín, Claudia Quezada
Glioblastoma multiforme (GBM) is considered the most common and aggressive tumour of the central nervous system and is characterized for being highly chemoresistant. This property is mainly due to the activation of Multiple Drug Resistance (MDR) mechanisms that protect cancer cells from structurally and morphologically different drugs. Overexpression and increased ABC transporters activity is one of the most important MDR mechanisms at the clinical level, and both its expression and activity are elevated in GBM cells...
February 20, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28217922/characterization-of-e-ntpdase-ec-3-6-1-5-activity-in-hepatic-lymphocytes-a-different-activity-profile-from-peripheral-lymphocytes
#19
Pedro H Doleski, Stephen A Adefegha, Fernanda L Cabral, Daniela B R Leal
The activity of ectonucleoside triphosphate diphosphohydrolase (E-NTPDase; EC 3.6.1.5) was characterized in hepatic lymphocytes (HL) of rats. For this purpose, a specific method for the isolation of lymphocytes from hepatic tissue was developed. Subsequently, E-NTPDase activity of rat HL was compared with that of rat peripheral lymphocytes. The HL showed high cell count and viability. Also, the characterization test revealed that the optimal E-NTPDase activities were attained at 37°C and pH 8.0 in the presence of Ca(2+) ...
March 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28214986/astrocyte-sodium-signalling-and-panglial-spread-of-sodium-signals-in-brain-white-matter
#20
Behrouz Moshrefi-Ravasdjani, Evelyn L Hammel, Karl W Kafitz, Christine R Rose
In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum...
February 18, 2017: Neurochemical Research
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