Introduction: P2 Receptors
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P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells
fphar-09-00149 February 26, 2018 Time: 17:57 # 1 ORIGINAL RESEARCH published: 28 February 2018 doi: 10.3389/fphar.2018.00149 P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells Mabrouka Salem1,2, Alain Tremblay2, Julie Pelletier2, Bernard Robaye3 and Jean Sévigny1,2* 1 Département de Microbiologie-Infectiologie et d’Immunologie, Faculté de Médecine, Université Laval, Québec City, QC, Canada, 2 Centre de Recherche du CHU de Québec – Université Laval, Québec City, QC, Canada, 3 Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP- 2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y6 receptors. qRT-PCR experiments showed that P2Y6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y6 Edited by: ligand UDP induced expression and secretion of CXCL10. For the other studies, we Kenneth A. Jacobson, −=− National Institutes of Health (NIH), took advantage of mice deficient in P2Y6 (P2ry6 ). Similar expression levels of P2Y1, −=− United States P2Y2, P2X2, P2X4, and A2A were detected in P2ry6 and WT IEC. Agonists of Reviewed by: TLR3 (poly(I:C)), TLR4 (LPS), P2Y1, and P2Y2 increased the expression and secretion Fernando Ochoa-Cortes, of CXCL10 more prominently in P2ry6−=− IEC than in WT IEC. CXCL10 expression Universidad Autónoma de San Luis −=− Potosí, Mexico and secretion induced by poly(I:C) in both P2ry6 and WT IEC were inhibited by Markus Neurath, general P2 antagonists (suramin and Reactive-Blue-2), by apyrase, and by specific Universitätsklinikum Erlangen, Germany antagonists of P2Y1, P2Y2, P2Y6 (only in WT), and P2X4. -
Effect of Theophylline and Enprofylline on Bronchial Hyperresponsiveness
Thorax: first published as 10.1136/thx.44.12.1022 on 1 December 1989. Downloaded from Thorax 1989;44:1022-1026 Effect of theophylline and enprofylline on bronchial hyperresponsiveness G H KOETER, J KRAAN, M BOORSMA, J H G JONKMAN, TH W VAN DER MARK From the Department ofPulmonology and Lung Function, University Hospital, Groningen; Pharma Bio Research, Assen; and Astra Pharmaceutica, Rijswijk, The Netherlands ABSTRACT The effect of increasing intravenous doses of theophylline and enprofylline, a new xanthine derivative, on bronchial responsiveness to methacholine was studied in eight asthmatic patients. Methacholine provocations were carried out on three days before and after increasing doses of theophylline, enprofylline, and placebo, a double blind study design being used. Methacholine responsiveness was determined as the provocative concentration of methacholine causing a fall of 20% in FEV, (PC20). The patients were characterised pharmacokinetically before the main study to provide an individual dosage scheme for each patient that would provide rapid steady state plasma concentration plateaus of 5, 10, and 15 mg/l for theophylline and 1 25, 2 5, and 3-75 mg/l for enprofylline. Dose increments in the main study were given at 90 minute intervals. FEV, showed a small progressive decrease after placebo; it remained high in relation to placebo after both drugs and this effect was dose related. Methacholine PC20 values decreased after placebo; mean values were (maximum difference 2-0 and 1 7 higher after theophylline and enprofylline than after placebo copyright. doubling doses of methacholine); the effect of both drugs was dose related. Thus enprofylline and theophylline when given intravenously cause a small dose related increase in FEV1 and methacholine PC20 when compared with placebo. -
P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases
International Journal of Molecular Sciences Review P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases Derek Strassheim 1, Alexander Verin 2, Robert Batori 2 , Hala Nijmeh 3, Nana Burns 1, Anita Kovacs-Kasa 2, Nagavedi S. Umapathy 4, Janavi Kotamarthi 5, Yash S. Gokhale 5, Vijaya Karoor 1, Kurt R. Stenmark 1,3 and Evgenia Gerasimovskaya 1,3,* 1 The Department of Medicine Cardiovascular and Pulmonary Research Laboratory, University of Colorado Denver, Aurora, CO 80045, USA; [email protected] (D.S.); [email protected] (N.B.); [email protected] (V.K.); [email protected] (K.R.S.) 2 Vascular Biology Center, Augusta University, Augusta, GA 30912, USA; [email protected] (A.V.); [email protected] (R.B.); [email protected] (A.K.-K.) 3 The Department of Pediatrics, Division of Critical Care Medicine, University of Colorado Denver, Aurora, CO 80045, USA; [email protected] 4 Center for Blood Disorders, Augusta University, Augusta, GA 30912, USA; [email protected] 5 The Department of BioMedical Engineering, University of Wisconsin, Madison, WI 53706, USA; [email protected] (J.K.); [email protected] (Y.S.G.) * Correspondence: [email protected]; Tel.: +1-303-724-5614 Received: 25 August 2020; Accepted: 15 September 2020; Published: 18 September 2020 Abstract: Purinergic G-protein-coupled receptors are ancient and the most abundant group of G-protein-coupled receptors (GPCRs). The wide distribution of purinergic receptors in the cardiovascular system, together with the expression of multiple receptor subtypes in endothelial cells (ECs) and other vascular cells demonstrates the physiological importance of the purinergic signaling system in the regulation of the cardiovascular system. -
NIH Public Access Author Manuscript Neuron Glia Biol
NIH Public Access Author Manuscript Neuron Glia Biol. Author manuscript; available in PMC 2006 May 1. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Neuron Glia Biol. 2006 May ; 2(2): 125±138. Purinergic receptors activating rapid intracellular Ca2+ increases in microglia Alan R. Light1, Ying Wu2, Ronald W. Hughen1, and Peter B. Guthrie3 1 Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA 2 Oral Biology Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27510, USA 3 Scientific Review Administrator, Center for Scientific Review, National Institutes of Health, 6701 Rockledge Drive, Room 4142 Msc 7850, Bethesda, MD 20892-7850, USA Abstract We provide both molecular and pharmacological evidence that the metabotropic, purinergic, P2Y6, P2Y12 and P2Y13 receptors and the ionotropic P2X4 receptor contribute strongly to the rapid calcium response caused by ATP and its analogues in mouse microglia. Real-time PCR demonstrates that the most prevalent P2 receptor in microglia is P2Y6 followed, in order, by P2X4, P2Y12, and P2X7 = P2Y13. Only very small quantities of mRNA for P2Y1, P2Y2, P2Y4, P2Y14, P2X3 and P2X5 were found. Dose-response curves of the rapid calcium response gave a potency order of: 2MeSADP>ADP=UDP=IDP=UTP>ATP>BzATP, whereas A2P4 had little effect. Pertussis toxin partially blocked responses to 2MeSADP, ADP and UDP. The P2X4 antagonist suramin, but not PPADS, significantly blocked responses to ATP. These data indicate that P2Y6, P2Y12, P2Y13 and P2X receptors mediate much of the rapid calcium responses and shape changes in microglia to low concentrations of ATP, presumably at least partly because ATP is rapidly hydrolyzed to ADP. -
Vitamin B6 Metabolism and Regulation of Pyridoxal Kinase
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2009 VITAMIN B6 METABOLISM AND REGULATION OF PYRIDOXAL KINASE Amit Gandhi Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Chemicals and Drugs Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2008 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Amit K. Gandhi 2009 All Rights Reserved VITAMIN B 6 METABOLISM AND REGULATION OF PYRIDOXAL KINASE A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. By AMIT K. GANDHI M.S (Pharmaceutical Science), Rajiv Gandhi University, Indore, India, 2003 B.Pharm, Rajiv Gandhi University, Indore, India, 2001 Director: Martin K. Safo, Ph.D Assistant Professor, Department of Medicinal Chemistry Virginia Commonwealth University Richmond, Virginia December, 2009 Acknowledgement I would like to take this opportunity to express my deep gratitude and profound respect to my advisor, Dr. Martin K. Safo, for his supervision, advice, and guidance in this research work. His support and insight have been invaluable in the progression of my research. I also appreciate his words of encouragement, which kept me always in an innovative mood and guided me at all the times to bring about the best in me. He is my mentor and teacher whom I shall remember forever. -
Evaluation of Bitter Kola Leaf Extract As an Anticorrosion Additive for Mild
RESEARCH ARTICLE V.C. Anadebe, P.C. Nnaji, N.A. Okafor, J.O. Ezeugo, F.E. Abeng and O.D. Onukwuli, 6 S. Afr. J. Chem., 2021, 75, 6–17, <https://journals.co.za/content/journal/chem/>. Evaluation of Bitter Kola Leaf Extract as an Anticorrosion Additive for Mild Steel in 1.2 M H2SO4 Electrolyte Valentine Chikaodili Anadebea,* §, Patrick Chukwudi Nnajib, Nkechinyere Amaka Okaforc, Joseph Okechukwu Ezeugoc, Fidelis Ebunta Abengd and Okechukwu Dominic Onukwulie aDepartment of Chemical Engineering, Federal University Ndufu Alike, Ebonyi State, Nigeria. bDepartment of Chemical Engineering, Michael Okpara University of Agriculture, Abia State, Nigeria. cDepartment of Chemical Engineering, Chukwuemeka Odumegwu Ojukwu University, Nigeria. dMaterial and Electrochemistry Unit, Department. of Chemistry, Cross River University of Technology, Calabar, Nigeria. eDepartment of Chemical Engineering, Nnamdi Azikwe University Awka, Anambra State, Nigeria. Received 24 January 2020, revised 29 August 2020, accepted 29 August 2020. ABSTRACT Plant-based material, namely bitter kola leaf, as an additive for surface modification of mild steel in H2SO4 solution was thoroughly scrutinized using electrochemical, theoretical and optimization techniques. The functional groups, of the biomolecules of the bitter kola leaf extract, were examined using Fourier transform infrared spectrometry (FTIR) and gas chroma- tography-mass spectrophotometry (GC-MS). For clarification purpose, scanning electron microscopy (SEM) was used to inspect the texture of the degraded and inhibited steel after 21 h of immersion. For the response surface methodology (RSM), central composite design of Design-Expert Software was used to optimize the inhibition efficiency as a function of acid concentration, inhibitor concentration, temperature and time. The optimum inhibition efficiency of 93 % was obtained at 0.9 g L–1 bitter kola leaf. -
Modulatory Roles of ATP and Adenosine in Cholinergic Neuromuscular Transmission
International Journal of Molecular Sciences Review Modulatory Roles of ATP and Adenosine in Cholinergic Neuromuscular Transmission Ayrat U. Ziganshin 1,* , Adel E. Khairullin 2, Charles H. V. Hoyle 1 and Sergey N. Grishin 3 1 Department of Pharmacology, Kazan State Medical University, 49 Butlerov Street, 420012 Kazan, Russia; [email protected] 2 Department of Biochemistry, Laboratory and Clinical Diagnostics, Kazan State Medical University, 49 Butlerov Street, 420012 Kazan, Russia; [email protected] 3 Department of Medical and Biological Physics with Computer Science and Medical Equipment, Kazan State Medical University, 49 Butlerov Street, 420012 Kazan, Russia; [email protected] * Correspondence: [email protected]; Tel.: +7-843-236-0512 Received: 30 June 2020; Accepted: 1 September 2020; Published: 3 September 2020 Abstract: A review of the data on the modulatory action of adenosine 5’-triphosphate (ATP), the main co-transmitter with acetylcholine, and adenosine, the final ATP metabolite in the synaptic cleft, on neuromuscular transmission is presented. The effects of these endogenous modulators on pre- and post-synaptic processes are discussed. The contribution of purines to the processes of quantal and non- quantal secretion of acetylcholine into the synaptic cleft, as well as the influence of the postsynaptic effects of ATP and adenosine on the functioning of cholinergic receptors, are evaluated. As usual, the P2-receptor-mediated influence is minimal under physiological conditions, but it becomes very important in some pathophysiological situations such as hypothermia, stress, or ischemia. There are some data demonstrating the same in neuromuscular transmission. It is suggested that the role of endogenous purines is primarily to provide a safety factor for the efficiency of cholinergic neuromuscular transmission. -
Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS
cells Review Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS Peter Illes 1,2,*, Patrizia Rubini 2, Henning Ulrich 3, Yafei Zhao 4 and Yong Tang 2,4 1 Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, Germany 2 International Collaborative Centre on Big Science Plan for Purine Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; [email protected] (P.R.); [email protected] (Y.T.) 3 Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 748, Brazil; [email protected] 4 Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; [email protected] * Correspondence: [email protected]; Tel.: +49-34-1972-46-14 Received: 17 March 2020; Accepted: 27 April 2020; Published: 29 April 2020 Abstract: Microglial cells, the resident macrophages of the central nervous system (CNS), exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell-damaging factors, they get transformed into an amoeboid phenotype releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species, and the excytotoxic ATP and glutamate. In addition, they engulf pathogenic bacteria or cell debris and phagocytose them. However, already resting/surveying microglia have a number of important physiological functions in the CNS; for example, they shield small disruptions of the blood–brain barrier by their processes, dynamically interact with synaptic structures, and clear surplus synapses during development. In neurodegenerative illnesses, they aggravate the original disease by a microglia-based compulsory neuroinflammatory reaction. -
Purinergic Receptors Brian F
Chapter 21 Purinergic receptors Brian F. King and Geoffrey Burnstock 21.1 Introduction The term purinergic receptor (or purinoceptor) was first introduced to describe classes of membrane receptors that, when activated by either neurally released ATP (P2 purinoceptor) or its breakdown product adenosine (P1 purinoceptor), mediated relaxation of gut smooth muscle (Burnstock 1972, 1978). P2 purinoceptors were further divided into five broad phenotypes (P2X, P2Y, P2Z, P2U, and P2T) according to pharmacological profile and tissue distribution (Burnstock and Kennedy 1985; Gordon 1986; O’Connor et al. 1991; Dubyak 1991). Thereafter, they were reorganized into families of metabotropic ATP receptors (P2Y, P2U, and P2T) and ionotropic ATP receptors (P2X and P2Z) (Dubyak and El-Moatassim 1993), later redefined as extended P2Y and P2X families (Abbracchio and Burnstock 1994). In the early 1990s, cDNAs were isolated for three heptahelical proteins—called P2Y1, P2Y2, and P2Y3—with structural similarities to the rhodopsin GPCR template. At first, these three GPCRs were believed to correspond to the P2Y, P2U, and P2T receptors. However, the com- plexity of the P2Y receptor family was underestimated. At least 15, possibly 16, heptahelical proteins have been associated with the P2Y receptor family (King et al. 2001, see Table 21.1). Multiple expression of P2Y receptors is considered the norm in all tissues (Ralevic and Burnstock 1998) and mixtures of P2 purinoceptors have been reported in central neurones (Chessell et al. 1997) and glia (King et al. 1996). The situation is compounded by P2Y protein dimerization to generate receptor assemblies with subtly distinct pharmacological proper- ties from their constituent components (Filippov et al. -
Adenosine Receptors and Endothelial Cell Mediated Wound Healing
Adenosine Receptors And Endothelial Cell Mediated Wound Healing Author Bonyanian, Zeinab Published 2017 Thesis Type Thesis (PhD Doctorate) School School of Medical Science DOI https://doi.org/10.25904/1912/1773 Copyright Statement The author owns the copyright in this thesis, unless stated otherwise. Downloaded from http://hdl.handle.net/10072/367912 Griffith Research Online https://research-repository.griffith.edu.au Adenosine Receptors And Endothelial Cell Mediated Wound Healing Zeinab Bonyanian BSc, MSc School of Medical Science Griffith Health Griffith University Submitted in fulfilment of the requirements of the degree of Doctor of Philosophy February 2017 1 STATEMENT OF ORIGINALITY This work has not previously been submitted for a degree or diploma in any university. To the best of my knowledge and belief, the thesis contains no material previously published or written by another person except where due reference is made in the thesis itself. Zeinab Bonyanian (Zina) 2 ACKNOWLEDGEMENT Firstly, I would like to express my sincere gratitude to my principal advisor, Associate Professor Roselyn Rose’Meyer, for the continuous support of my Ph.D study and related research, for her patience, motivation, and immense knowledge. Her guidance helped me during both the research and writing of this thesis. I could not imagine having a better supervisor and mentor for my Ph.D study. I would also like to acknowledge Associate Professor Joss Du Toit, my associate supervisor, and Professor David Shum for their support. I am very thankful to Dr. Janet Hussein for providing me with professional guidance and useful advice on my thesis writing. Many thanks to my friend Ms. -
Pharmaceuticals 2010, 3, 725-747; Doi:10.3390/Ph3030725
Pharmaceuticals 2010, 3, 725-747; doi:10.3390/ph3030725 OPEN ACCESS pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Review Theophylline Peter J. Barnes National Heart and Lung Institute, Imperial College, London, UK; E-Mail: [email protected]; Tel.: +44-207-351-8174; Fax: +44-207-351-5675. Received: 14 January 2010 / Accepted: 18 March 2010 / Published: 18 March 2010 Abstract: Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have anti-inflammatory effects in asthma and COPD at lower concentrations. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Through this mechanism theophylline also reverses corticosteroid resistance and this may be of particular value in severe asthma and COPD where HDAC2 activity is markedly reduced. Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma) and blood concentrations are determined mainly by hepatic metabolism, which may be increased or decreased in several diseases and by concomitant drug therapy. Theophylline is now usually used as an add-on therapy in asthma patients not well controlled on inhaled corticosteroids and in COPD patients with severe disease not controlled by bronchodilator therapy. -
Glutamatergic and Purinergic Receptor-Mediated Calcium Transients in Bergmann Glial Cells
The Journal of Neuroscience, April 11, 2007 • 27(15):4027–4035 • 4027 Cellular/Molecular Glutamatergic and Purinergic Receptor-Mediated Calcium Transients in Bergmann Glial Cells Richard Piet and Craig E. Jahr Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239 2ϩ Astrocytesrespondtoneuronalactivitywith[Ca ]i increasesafteractivationofspecificreceptors.Bergmannglialcells(BGs),astrocytes of the cerebellar molecular layer (ML), express various receptors that can mobilize internal Ca 2ϩ. BGs also express Ca 2ϩ permeable AMPA receptors that may be important for maintaining the extensive coverage of Purkinje cell (PC) excitatory synapses by BG processes. Here, we examined Ca 2ϩ signals in single BGs evoked by synaptic activity in cerebellar slices. Short bursts of high-frequency stimulation of the ML elicited Ca 2ϩ transients composed of a small-amplitude fast rising phase, followed by a larger and slower rising phase. The first phase resulted from Ca 2ϩ influx through AMPA receptors, whereas the second phase required release of Ca 2ϩ from internal stores initiated by P2 purinergic receptor activation. We found that such Ca 2ϩ responses could be evoked by direct activation of neurons releasing ATP onto BGs or after activation of metabotropic glutamate receptor 1 on these neurons. Moreover, examination of BG and PC responses to various synaptic stimulation protocols suggested that ML interneurons are likely the cellular source of ATP. Key words: cerebellum; neuron–glia interaction; ATP; AMPA receptors; mGluR1; synaptic