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Therapeutic Targets for the Treatment of Chronic Cough
Therapeutic Targets for the Treatment of Chronic Cough Roe, N., Lundy, F., Litherland, G. J., & McGarvey, L. (2019). Therapeutic Targets for the Treatment of Chronic Cough. Current Otorhinolaryngology Reports. https://doi.org/10.1007/s40136-019-00239-9 Published in: Current Otorhinolaryngology Reports Document Version: Publisher's PDF, also known as Version of record Queen's University Belfast - Research Portal: Link to publication record in Queen's University Belfast Research Portal Publisher rights Copyright 2019 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made to ensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws. If you discover content in the Research Portal that you believe breaches copyright or violates any law, please contact [email protected]. Download date:25. Sep. 2021 Current Otorhinolaryngology Reports https://doi.org/10.1007/s40136-019-00239-9 CHRONIC COUGH (K ALTMAN, SECTION EDITOR) Therapeutic Targets for the Treatment of Chronic Cough N. -
Advancing Basic Pain Research
The Rita Allen Foundation AWARD IN PAIN SCHOLARS: ADVANCING BASIC PAIN RESEARCH AWARD IN PAIN SCHOLARS: ADVANCING BASIC PAIN RESEARCH 1 COVER: Tuan Trang, a 2014 Rita Allen Foundation Scholar, has investigated mechanisms of opioid tolerance and withdrawal. Trang and his research group have found that immune cells in the central nervous system, known as microglia, play a key role in the development of morphine tolerance in an animal model. This image, a compilation of spinal microglia forming a cross section of the lumbar spinal cord, appeared on the cover of the October 18, 2017, issue of The Journal of Neuroscience in conjunction with the research article “Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance.” (Image by Heather Leduc-Pessah, Trang Laboratory) A NETWORK OF HOPE Created in 2009 to expand the reach of the Rita Allen Foundation Scholars program, the Award in Pain has now supported 29 pioneering early-career Pain Scholars. Each year, as we welcome our newest class of Scholars, we reflect on the accomplishments of this growing community of researchers and the profound questions that drive them forward to new discoveries. These scientists are leading efforts to understand the complex neurobiological mechanisms that underlie pain—including mapping the neural circuits of chronic pain, defining the Elizabeth G. Christopherson roles of immune signals, and examining the connections President and between pain and itch. Their findings point to approaches for Chief Executive Officer combating opioid tolerance and withdrawal, interventions Rita Allen Foundation to interrupt the transition from acute to chronic pain after injury, and targets for completely novel pain therapies with the potential to improve safety and specificity. -
Therapeutic Targets for the Treatment of Chronic Cough
Current Otorhinolaryngology Reports https://doi.org/10.1007/s40136-019-00239-9 CHRONIC COUGH (K ALTMAN, SECTION EDITOR) Therapeutic Targets for the Treatment of Chronic Cough N. A. Roe1 & F. T. Lundy1 & G. J. Litherland2 & L. P. A. McGarvey1 # The Author(s) 2019 Abstract Purpose of Review Chronic cough, defined in adults as one lasting longer than 8 weeks, is among the commonest clinical problems encountered by doctors both in general practice and in hospital. It can exist as a distinct clinical problem or as a prominent and troublesome symptom for patients with common pulmonary conditions including asthma, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Recent Findings Chronic cough impacts considerably on patients’ daily-life activities and many patients are left frustrated by what they see as a complete lack of awareness among their doctors as how to treat their condition. Some of this arises from limited levels of physician knowledge about managing cough as a clinical problem but also because there are no very effective treatments that specifically target cough. Summary In this article, we review the current clinical thinking regarding cough and the treatments that are currently used and those undergoing clinical development. Keywords Cough . Cough receptor . Pharmacological targets . Novel . Ion channel Introduction and is likely due to a slowly resolving post-viral cough. In adult patients, a cough persisting for more than 8 weeks is Under normal physiological circumstances, coughing occurs termed ‘chronic’ and can occur as an isolated clinical problem with the primary purpose of protecting the lung from inhaled or associated with common respiratory and non-respiratory irritants and clearing unwanted airway secretions. -
The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels
ORIGINAL RESEARCH published: 23 January 2019 doi: 10.3389/fphar.2019.00006 The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels Sara Baratchi 1*, Peter Keov 1,2,3, William G. Darby 1, Austin Lai 1, Khashayar Khoshmanesh 4, Peter Thurgood 4, Parisa Vahidi 1, Karin Ejendal 5 and Peter McIntyre 1 1 School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia, 2 Molecular Pharmacology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia, 3 St Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, Australia, 4 School of Engineering, RMIT University, Melbourne, VIC, Australia, 5 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States TRPV4 is a non-selective cation channel that tunes the function of different tissues including the vascular endothelium, lung, chondrocytes, and neurons. GSK1016790A is the selective and potent agonist of TRPV4 and a pharmacological tool that is used to study the TRPV4 physiological function in vitro and in vivo. It remains unknown how the sensitivity of TRPV4 to this agonist is regulated. The spatial and temporal dynamics of receptors are the major determinants of cellular responses to stimuli. Membrane Edited by: Hugues Abriel, translocation has been shown to control the response of several members of the transient University of Bern, Switzerland receptor potential (TRP) family of ion channels to different stimuli. Here, we show that 2+ Reviewed by: TRPV4 stimulation with GSK1016790A caused an increase in [Ca ]i that is stable for Osama F. Harraz, a few minutes. Single molecule analysis of TRPV4 channels showed that the density University of Vermont, United States Irene Frischauf, of TRPV4 at the plasma membrane is controlled through two modes of membrane Johannes Kepler University of Linz, trafficking, complete, and partial vesicular fusion. -
Note: the Letters 'F' and 'T' Following the Locators Refers to Figures and Tables
Index Note: The letters ‘f’ and ‘t’ following the locators refers to figures and tables cited in the text. A Acyl-lipid desaturas, 455 AA, see Arachidonic acid (AA) Adenophostin A, 71, 72t aa, see Amino acid (aa) Adenosine 5-diphosphoribose, 65, 789 AACOCF3, see Arachidonyl trifluoromethyl Adlea, 651 ketone (AACOCF3) ADP, 4t, 10, 155, 597, 598f, 599, 602, 669, α1A-adrenoceptor antagonist prazosin, 711t, 814–815, 890 553 ADPKD, see Autosomal dominant polycystic aa 723–928 fragment, 19 kidney disease (ADPKD) aa 839–873 fragment, 17, 19 ADPKD-causing mutations Aβ, see Amyloid β-peptide (Aβ) PKD1 ABC protein, see ATP-binding cassette protein L4224P, 17 (ABC transporter) R4227X, 17 Abeele, F. V., 715 TRPP2 Abbott Laboratories, 645 E837X, 17 ACA, see N-(p-amylcinnamoyl)anthranilic R742X, 17 acid (ACA) R807X, 17 Acetaldehyde, 68t, 69 R872X, 17 Acetic acid-induced nociceptive response, ADPR, see ADP-ribose (ADPR) 50 ADP-ribose (ADPR), 99, 112–113, 113f, Acetylcholine-secreting sympathetic neuron, 380–382, 464, 534–536, 535f, 179 537f, 538, 711t, 712–713, Acetylsalicylic acid, 49t, 55 717, 770, 784, 789, 816–820, Acrolein, 67t, 69, 867, 971–972 885 Acrosome reaction, 125, 130, 301, 325, β-Adrenergic agonists, 740 578, 881–882, 885, 888–889, α2 Adrenoreceptor, 49t, 55, 188 891–895 Adult polycystic kidney disease (ADPKD), Actinopterigy, 223 1023 Activation gate, 485–486 Aframomum daniellii (aframodial), 46t, 52 Leu681, amino acid residue, 485–486 Aframomum melegueta (Melegueta pepper), Tyr671, ion pathway, 486 45t, 51, 70 Acute myeloid leukaemia and myelodysplastic Agelenopsis aperta (American funnel web syndrome (AML/MDS), 949 spider), 48t, 54 Acylated phloroglucinol hyperforin, 71 Agonist-dependent vasorelaxation, 378 Acylation, 96 Ahern, G. -
Transient Receptor Potential Vanilloid 4 Channel Deficiency Aggravates Tubular Damage After Acute Renal Ischaemia Reperfusion
www.nature.com/scientificreports OPEN Transient Receptor Potential Vanilloid 4 Channel Defciency Aggravates Tubular Damage after Received: 29 March 2017 Accepted: 5 March 2018 Acute Renal Ischaemia Reperfusion Published: xx xx xxxx Marwan Mannaa1, Lajos Markó2, András Balogh2,3,4, Emilia Vigolo5, Gabriele N’diaye2, Mario Kaßmann1, Laura Michalick6, Ulrike Weichelt6, Kai M. Schmidt–Ott5, Wolfgang B. Liedtke7, Yu Huang8,9, Dominik N. Müller 2,5, Wolfgang M. Kuebler6 & Maik Gollasch1,2 Transient receptor potential vanilloid 4 (TRPV4) cation channels are functional in all renal vascular segments and mediate endothelium-dependent vasorelaxation. Moreover, they are expressed in distinct parts of the tubular system and activated by cell swelling. Ischaemia/reperfusion injury (IRI) is characterized by tubular injury and endothelial dysfunction. Therefore, we hypothesised a putative organ protective role of TRPV4 in acute renal IRI. IRI was induced in TRPV4 defcient (Trpv4 KO) and wild–type (WT) control mice by clipping the left renal pedicle after right–sided nephrectomy. Serum creatinine level was higher in Trpv4 KO mice 6 and 24 hours after ischaemia compared to WT mice. Detailed histological analysis revealed that IRI caused aggravated renal tubular damage in Trpv4 KO mice, especially in the renal cortex. Immunohistological and functional assessment confrmed TRPV4 expression in proximal tubular cells. Furthermore, the tubular damage could be attributed to enhanced necrosis rather than apoptosis. Surprisingly, the percentage of infltrating granulocytes and macrophages were comparable in IRI–damaged kidneys of Trpv4 KO and WT mice. The present results suggest a renoprotective role of TRPV4 during acute renal IRI. Further studies using cell–specifc TRPV4 defcient mice are needed to clarify cellular mechanisms of TRPV4 in IRI. -
TRP CHANNELS AS THERAPEUTIC TARGETS TRP CHANNELS AS THERAPEUTIC TARGETS from Basic Science to Clinical Use
TRP CHANNELS AS THERAPEUTIC TARGETS TRP CHANNELS AS THERAPEUTIC TARGETS From Basic Science to Clinical Use Edited by ARPAD SZALLASI MD, PHD Department of Pathology, Monmouth Medical Center, Long Branch, NJ, USA AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London, EC2Y 5AS, UK 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 225 Wyman Street, Waltham, MA 02451, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK First published 2015 Copyright © 2015 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangement with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. -
Application Note Activation and Inhibition of TRPV4 Using Different
Channel: hTRPV4 Application Note Cells: CHO Tools: Port-a-Patch Activation and inhibition of TRPV4 using different stimuli on the Port-a-Patch The electrophysiology team at Nanion Technologies GmbH, Munich. Summary Results TRPV4 is a member of the transient receptor potential TRPV4 can be activated by a number of stimuli, includ- channel (TRP) family. Transient receptor potential vanilloid ing warm temperature >27°C6,7. We activated hTRPV4 type 4 (TRPV4) shares approximately 40% identity with expressed in CHO cells using heated solution at 45°C. TRPV1 and TRPV21 and is a Ca2+-permeable non-selective There was some basal activity of TRPV4 at room tempera- cation channel1-3 expressed in a wide range of tissues ture but the current amplitude increased to 5.7 ± 0.8 nA including neurons of the central and peripheral nervous (n = 6) from control current of 2.7 ± 0.6 nM (n = 6; p<0.01, systems, and in non-neuronal tissue including human T Student’s t test). Figure 1 shows the activation of TRPV4 by cells, corneal and retinal epithelial cells, endothelial cells warm solution from an example cell and the timecourse of the eye, liver, heart, kidney, synoviocytes, epithelial of the experiment. lining of trachea and lung airways, stellate cells of the A RT pancreas, and many more2. TRPV4 is activated by a 45°C number of stimuli including endogenous ligands such as lipid arachidonic acid and its metabolites4, synthetic ligands such as GSK1016790A5, warm temperature >27- 35°C6,7, hypotonic extracellular solution (cell swelling)1,8, and mechanical stress2. Given its widespread distribution in many organs, this suggests that TRPV4 plays a major role in many physiological processes2,9. -
Ion Channels
UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. -
GSK1016790A, a Novel and Potent TRPV4 Channel Agonist Induces Urinary Bladder Contraction and Hyperactivity
JPET Fast Forward. Published on May 22, 2008 as DOI: 10.1124/jpet.108.139295 JPETThis Fast article Forward. has not been Published copyedited andon formatted. May 22, The 2008 final asversion DOI:10.1124/jpet.108.139295 may differ from this version. JPET #139295 Title Page GSK1016790A, a Novel and Potent TRPV4 Channel Agonist Induces Urinary Bladder Contraction and Hyperactivity: Part I Downloaded from Kevin S. Thorneloe, Anthony C. Sulpizio, Zuojun Lin, David J. Figueroa, Angela K. Clouse, Gerald P. McCafferty, Tim P. Chendrimada, Erin S.R. Lashinger, Earl jpet.aspetjournals.org A. Gordon, Louise Evans, Blake A. Misajet, Douglas J. DeMarini, Josephine H. Nation, Linda N. Casillas, Robert W. Marquis, Bartholomew J. Votta, Steven A. at ASPET Journals on September 27, 2021 Sheardown, Xiaoping Xu, David P. Brooks, Nicholas J. Laping, and Timothy D. Westfall Cardiovascular and Urogenital Centre of Excellence in Drug Discovery (KST, ACS, ZL, DJF, AKC, GPM, TM, ESRL, EAG, LE, BAM, XX, CPB, NJL, TDW) GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA, USA, 19406; Oncology Centre of Excellence in Drug Discovery (DJD, LNC, RWM, BJV) GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, Collegeville, PA, USA, 19426; Transgenics, Genotyping and Viral Vectors (JHN, SAS), GlaxoSmithKline Pharmaceuticals, Harlow, UK CM19 5AD 1 Copyright 2008 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on May 22, 2008 as DOI: 10.1124/jpet.108.139295 This article has not been copyedited and formatted. The final version may differ from this version. JPET #139295 Running Title Page Running Title: TRPV4 activator GSK1016790A induces bladder overactivity Correspondence: Kevin S. -
(TRPM8) by Calcium-Rich Particulate Materials and Effects on Human
Molecular Pharmacology Fast Forward. Published on October 16, 2017 as DOI: 10.1124/mol.117.109959 This article has not been copyedited and formatted. The final version may differ from this version. MOL #109959 Title: Activation of Human Transient Receptor Potential Melastatin-8 (TRPM8) by Calcium- Rich Particulate Materials and Effects on Human Lung Cells Authors: John G. Lamb, Erin G. Romero, Zhenyu Lu, Seychelle K. Marcus, Hannah C. Peterson, John M. Veranth, Cassandra E. Deering-Rice, and Christopher A. Reilly Affiliations: (J.G.L., E.G.R., Z.L., S.K.M., H.C.P., J.M.V., C.E.D-R., and C.A.R.) Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, 30 S. 2000 E., Room 201 Skaggs Hall, Salt Lake City, UT 84112, USA. Downloaded from molpharm.aspetjournals.org at ASPET Journals on September 27, 2021 1 Molecular Pharmacology Fast Forward. Published on October 16, 2017 as DOI: 10.1124/mol.117.109959 This article has not been copyedited and formatted. The final version may differ from this version. MOL #109959 Running Title: Activation of TRPM8 by Particles *Corresponding author: Dr. Christopher A. Reilly, Ph.D. University of Utah Department of Pharmacology and Toxicology 30 South 2000 East, 201 Skaggs Hall Salt Lake City, UT 84112 Phone: (801) 581-5236; FAX: (801) 585-5111 Email: [email protected] Number of text pages: 41 Downloaded from Number of Tables: 2 Number of Figures: 7 References: 40 Number of words in Abstract: 245 Number of words in Introduction: 704 molpharm.aspetjournals.org Number -
Genetic Variation As a Tool for Identifying Novel Transducers of Itch
Genetic variation as a tool for identifying novel transducers of itch By Takeshi Morita A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Molecular and Cell Biology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Diana M. Bautista, Co-Chair Professor Rachel B. Brem, Co-Chair Professor John Ngai Professor Kristin Scott Professor Michael W. Nachman Summer 2016 Abstract Genetic variation as a tool for identifying novel transducers of itch by Takeshi Morita Doctor of Philosophy in Molecular and Cell Biology University of California, Berkeley Professor Diana M. Bautista, Co-Chair Professor Rachel B. Brem, Co-Chair The mammalian somatosensory system mediates itch, the irritating sensation that elicits a desire to scratch. Millions of people worldwide suffer from chronic itch that fails to respond to current drugs and therapies. Even though recent studies have begun to elucidate the basic characteristics of the itch circuitry, we have little understanding about the molecules and signaling mechanisms that underlie detection and transduction of itch sensation, especially during chronic itch conditions. We have taken a genomic approach by harnessing natural variation in itch-evoked scratching behaviors in mice to identify novel molecular players that are involved in itch signal transduction at the level of primary sensory neurons. From our analysis, we identified numerous candidate itch genes, and further identified a serotonin receptor, HTR7 as a key transducer that is required for both development and maintenance of chronic itch. We further investigated the genetic basis of variation in itch, and identified a set of genes and regulatory pathways that may be involved in controlling itch behaviors.