The Combined Effect of Branching and Elongation on the Bioactivity Profile of Phytocannabinoids
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1 TRP About Online
a TR P to Spain International Workshop on Transient Receptor Potential Channels 12th – 14th September 2012 Valencia, Spain www.trp2012.com SCHEDULE and ABSTRACTS BOOK September 2012 Dear participants, Travelling to faraway places in search of spiritual or cultural enlightenment is a millennium old human activity. In their travels, pilgrims brought with them news, foods, music and traditions from distant lands. This friendly exchange led to the cultural enrichment of visitors and the economic flourishing of places, now iconic, such as Rome, Santiago, Jerusalem, Mecca, Varanasi or Angkor Thom. The dissemination of science and technology also benefited greatly from these travels to remote locations. The new pilgrims of the Transient Receptor Potential (TRP) community are also very fond of travelling. In the past years they have gathered at various locations around the globe: Breckenridge (USA), Eilat (Israel), Stockholm (Sweden) and Leuven (Belgium) come to mind. These meetings, each different and exciting, have been very important for the dissemination of TRP research. We are happy to welcome you in Valencia (Spain) for TRP2012. The response to our call has been extraordinary, surpassing all our expectations. The speakers, the modern bards, readily attended our request to communicate their new results. At last count we were already more than 170 participants, many of them students, and most presenting their recent work in the form of posters or short oral presentations. At least 25 countries are sending TRP ambassadors to Valencia, making this a truly international meeting. We like to thank the staff of the Cátedra Santiago Grisolía, Fundación Ciudad de las Artes y las Ciencias for their dedication and excellence in handling the administrative details of the workshop. -
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. -
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. -
) (51) International Patent Classification: Columbia V5G 1G3
) ( (51) International Patent Classification: Columbia V5G 1G3 (CA). PANDEY, Nihar R.; 10209 A 61K 31/4525 (2006.01) C07C 39/23 (2006.01) 128A St, Surrey, British Columbia V3T 3E7 (CA). A61K 31/05 (2006.01) C07D 405/06 (2006.01) (74) Agent: ZIESCHE, Sonia et al.; Gowling WLG (Canada) A61P25/22 (2006.01) LLP, 2300 - 550 Burrard Street, Vancouver, British Colum¬ (21) International Application Number: bia V6C 2B5 (CA). PCT/CA2020/050165 (81) Designated States (unless otherwise indicated, for every (22) International Filing Date: kind of national protection av ailable) . AE, AG, AL, AM, 07 February 2020 (07.02.2020) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (25) Filing Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (26) Publication Language: English HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (30) Priority Data: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 16/270,389 07 February 2019 (07.02.2019) US OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (63) Related by continuation (CON) or continuation-in-part SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, (CIP) to earlier application: TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. US 16/270,389 (CON) (84) Designated States (unless otherwise indicated, for every Filed on 07 Februaiy 2019 (07.02.2019) kind of regional protection available) . -
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. -
Synthetic Cannabinoids (60 Substances) A) Classical Cannabinoid
Synthetic cannabinoids (60 substances) a) Classical cannabinoid OH H OH H O Common name Chemical name CAS number Molecular Formula HU-210 3-(1,1’-dimethylheptyl)-6aR,7,10,10aR-tetrahydro-1- Synonym: 112830-95-2 C H O hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol 25 38 3 11-Hydroxy-Δ-8-THC-DMH b) Nonclassical cannabinoids OH OH R2 R3 R4 R1 CAS Molecular Common name Chemical name R1 R2 R3 R4 number Formula rel-2[(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methyloctan- 2- yl) CP-47,497 70434-82-1 C H O CH H H H phenol 21 34 2 3 rel-2[(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methylheptan- 2- yl) CP-47,497-C6 - C H O H H H H phenol 20 32 2 CP-47,497-C8 rel-2- [(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methylnonan- 2- yl) 70434-92-3 C H O C H H H H Synonym: Cannabicyclohexanol phenol 22 36 2 2 5 CAS Molecular Common name Chemical name R1 R2 R3 R4 number Formula rel-2[(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methyldecan- 2- yl) CP-47,497-C9 - C H O C H H H H phenol 23 38 2 3 7 rel-2- ((1 R,2 R,5 R)-5- hydroxy- 2- (3- hydroxypropyl)cyclohexyl)- 3-hydroxy CP-55,940 83003-12-7 C H O CH H H 5-(2- methyloctan- 2- yl)phenol 24 40 3 3 propyl rel-2- [(1 S,3 R)-3- hydroxy-5,5-dimethylcyclohexyl]- 5- (2- Dimethyl CP-47,497-C8 - C H O C H CH CH H methylnonan-2- yl)phenol 24 40 2 2 5 3 3 c) Aminoalkylindoles i) Naphthoylindoles 1' R R3' R2' O N CAS Molecular Common name Chemical name R1’ R2’ R3’ number Formula [1-[(1- methyl- 2- piperidinyl)methyl]- 1 H-indol- 3- yl]- 1- 1-methyl-2- AM-1220 137642-54-7 C H N O H H naphthalenyl-methanone 26 26 2 piperidinyl -
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. -
Synthetic Cannabinoids, Forensic & Legal Aspects
Synthetic Cannabinoids, Forensic & Legal Aspects Marilyn A. Huestis, PhD Chief, Chemistry & Drug Metabolism National Institute on Drug Abuse, National Institutes of Health Council of Forensic Medicine Istanbul, Turkey August 18, 2011 Synthetic Cannabinoid Overview Cannabinoid pharmacology Chemistry of synthetic cannabinoids Metabolism of synthetic cannabinoids Controlled drug administration studies Analytical methods for the identification of synthetic cannabinoids in biological & non-biological matrices Current legal status of synthetic cannabinoids Cannabis Mechanisms of Action THC binds to cannabinoid receptors & modulates endogenous cannabinoid & other neurotransmitter systems CB-1 receptors primarily in central nervous & cardiovascular systems CB-2 receptors primarily in immune system Non-CB1, non-CB2 receptors G-protein receptors discovered & cloned in late 1980’s Endogenous cannabinoids include anandamide, 2-AG, virodhamine, N-arachidonyl dopamine (NADA), oleamide, 2-arachidonyl glyceryl ether (noladin ether) & others High CB1 Receptor Density Hypothalamus Appetite, Hormones & Sexual behavior Neocortex High cognitive function & Sensory data Basal Ganglia integration Motor control & planning Hippocampus Memory & Learning Amygdala Anxiety, Emotion & Fear Cerebellum Brain Stem Motor control & Spinal Cord & coordination Vomiting reflex & Pain sensation Cannabinoid Mechanisms of Action Receptor distribution in brain correlates with areas involved in physiological, psychomotor & cognitive effects High density in caudate -
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.