TRPV1: Structure, Endogenous Agonists, and Mechanisms
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Pepperspray, CS, & Other 'Less-Lethal' Weapons
CONTENTS: Protective Measures: p.26-27 Pepperspray: p.2-9, 14-15 Chemical Data Table: p.30 CS/CN: p.10-16 Risk Groups: p.14-15 When to do what / Other Gas Types: p. 12 Asthma: p.14 treatment algorithm: p.4 Rubber Bullets: p.19-21 Nightsticks/Batons: p.17 LAW: p.6 Concussion Grenades: p.22 CR: p.12 VOFIBA: p.7 Fear: p.24 CA: p.12 Making Remedies: p.13 Tasers: p.18 DM: p.12 Sample Card for Handing Out: Shamelessly adapted from the Black Cross Radical Health Collective, www.blackcrosscollective.org If your condition is worsening, go to an emergency room. Basic preparations: Stick with your buddy. Pepperspray, CS, & Other Work with an affinity group. Bring water. Vulnerable people like asthmatics may want to “Less-Lethal” Weapons (your logo here) avoid chemical weapons. You must remove small children from the area BEFORE Used by Rioting Police to Suppress Dissent chemical weapons are used. Check out our w h e n P o l i t r i c k s & Te l e v i s i o n f a i l t o d o s o . website <www.---.org> for lots more info on how to prepare. v3.3 Useful Numbers: Serious injuries: If you don’t know how to treat Medical Emergency: 911 an injury, get a medic, or call 911. Don’t treat Copwatch: 123-4560 someone if you don’t know how. If you are Convergence Ctr Aid Station:123-4567 injured by the police, get to a nurse practitioner, Aftercare Clinic: 123-4568 physician’s assistant, or doctor immediately Legal Team: 123-4565 and have your injury documented in case you Public Defenders: 123-4569 decide to sue. -
TRPM8 Activation by Menthol, Icilin, and Cold Is Differenially Modulated by Intracellular Ph
5364 • The Journal of Neuroscience, June 9, 2004 • 24(23):5364–5369 Cellular/Molecular TRPM8 Activation by Menthol, Icilin, and Cold Is Differentially Modulated by Intracellular pH David A. Andersson, Henry W. N. Chase, and Stuart Bevan Novartis Institute for Medical Sciences, London WC1E 6BN, United Kingdom TRPM8 is a nonselective cation channel activated by cold and the cooling compounds menthol and icilin (Peier et al., 2002). Here, we have used electrophysiology and the calcium-sensitive dye Fura-2 to study the effect of pH and interactions between temperature, pH, and the two chemical agonists menthol and icilin on TRPM8 expressed in Chinese hamster ovary cells. Menthol, icilin, and cold all evoked 2ϩ ϩ stimulus-dependent [Ca ]i responses in standard physiological solutions of pH 7.3. Increasing the extracellular [H ] from pH 7.3 to approximately pH 6 abolished responses to icilin and cold stimulation but did not affect responses to menthol. Icilin concentration– response curves were significantly shifted to the right when pH was lowered from 7.3 to 6.9, whereas those with menthol were unaltered in solutions of pH 6.1. When cells were exposed to solutions in the range of pH 8.1–6.5, the temperature threshold for activation was elevatedathigherpHanddepressedatlowerpH.Superfusingcellswithalowsubactivatingconcentrationoficilinormentholelevatedthe 2ϩ threshold for cold activation at pH 7.4, but cooling failed to evoke [Ca ]i responses at pH 6 in the presence of either agonist. In voltage-clamp experiments in which the intracellular pH was buffered to different levels, acidification reduced the current amplitude of icilin responses and shifted the threshold for cold activation to lower values with half-maximal inhibition at pH 7.2 and pH 7.6. -
TRP Mediation
molecules Review Remedia Sternutatoria over the Centuries: TRP Mediation Lujain Aloum 1 , Eman Alefishat 1,2,3 , Janah Shaya 4 and Georg A. Petroianu 1,* 1 Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates; [email protected] (L.A.); Eman.alefi[email protected] (E.A.) 2 Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates 3 Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman 11941, Jordan 4 Pre-Medicine Bridge Program, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates; [email protected] * Correspondence: [email protected]; Tel.: +971-50-413-4525 Abstract: Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants. -
Effect of Capsaicin and Other Thermo-TRP Agonists on Thermoregulatory Processes in the American Cockroach
Article Effect of Capsaicin and Other Thermo-TRP Agonists on Thermoregulatory Processes in the American Cockroach Justyna Maliszewska 1,*, Milena Jankowska 2, Hanna Kletkiewicz 1, Maria Stankiewicz 2 and Justyna Rogalska 1 1 Department of Animal Physiology, Faculty of Biology and Environmental Protection, Nicolaus Copernicus University, 87-100 Toruń, Poland; [email protected] (H.K.); [email protected] (J.R.) 2 Department of Biophysics, Faculty of Biology and Environmental Protection, Nicolaus Copernicus University, 87-100 Toruń, Poland; [email protected] (M.J.); [email protected] (M.S.) * Correspondence: [email protected]; Tel.: +48-56611-44-63 Academic Editor: Pin Ju Chueh Received: 5 November 2018; Accepted: 17 December 2018; Published: 18 December 2018 Abstract: Capsaicin is known to activate heat receptor TRPV1 and induce changes in thermoregulatory processes of mammals. However, the mechanism by which capsaicin induces thermoregulatory responses in invertebrates is unknown. Insect thermoreceptors belong to the TRP receptors family, and are known to be activated not only by temperature, but also by other stimuli. In the following study, we evaluated the effects of different ligands that have been shown to activate (allyl isothiocyanate) or inhibit (camphor) heat receptors, as well as, activate (camphor) or inhibit (menthol and thymol) cold receptors in insects. Moreover, we decided to determine the effect of agonist (capsaicin) and antagonist (capsazepine) of mammalian heat receptor on the American cockroach’s thermoregulatory processes. We observed that capsaicin induced the decrease of the head temperature of immobilized cockroaches. Moreover, the examined ligands induced preference for colder environments, when insects were allowed to choose the ambient temperature. -
Regulation of TRP Channels by Steroids
General and Comparative Endocrinology xxx (2014) xxx–xxx Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen Review Regulation of TRP channels by steroids: Implications in physiology and diseases ⇑ Ashutosh Kumar, Shikha Kumari, Rakesh Kumar Majhi, Nirlipta Swain, Manoj Yadav, Chandan Goswami School of Biology, National Institute of Science Education and Research, Sachivalaya Marg, Bhubaneswar, Orissa 751005, India article info abstract Article history: While effects of different steroids on the gene expression and regulation are well established, it is proven Available online xxxx that steroids can also exert rapid non-genomic actions in several tissues and cells. In most cases, these non-genomic rapid effects of steroids are actually due to intracellular mobilization of Ca2+- and other ions Keywords: suggesting that Ca2+ channels are involved in such effects. Transient Receptor Potential (TRP) ion TRP channels channels or TRPs are the largest group of non-selective and polymodal ion channels which cause Ca2+- Steroids influx in response to different physical and chemical stimuli. While non-genomic actions of different Non-genomic action of steroids steroids on different ion channels have been established to some extent, involvement of TRPs in such Ca2+-influx functions is largely unexplored. In this review, we critically analyze the literature and summarize how Expression different steroids as well as their metabolic precursors and derivatives can exert non-genomic effects by acting on different TRPs qualitatively and/or quantitatively. Such effects have physiological repercus- sion on systems such as in sperm cells, immune cells, bone cells, neuronal cells and many others. -
102 the Effects of Intravesical
102 Harper M, Brady C. M, Scaravilli F, Fowler C. J. Institute of Neurology, London THE EFFECTS OF INTRAVESICAL RESINIFERATOXIN ON SUBUROTHELIAL NERVE DENSITY IN PATIENTS WITH NEUROGENIC DETRUSOR OVERACTIVITY Aims of Study Somatic and autonomic neural pathways integrated in the CNS regulate urine storage and voiding. When spinal cord lesions disrupt these pathways, an aberrant segmental sacral reflex emerges, the afferent limb of which is comprised of small unmyelinated C-fibres that originate in the suburothelium. This pathological reflex is thought to be the underlying cause of “spinal” neurogenic detrusor overactivity (NDO). We are currently evaluating the role of resiniferatoxin (RTX) in the treatment of refractory “spinal” NDO. RTX is an ultra-potent capsaicin analogue purified from the dried latex of the succulent plant Euphorbia Resinifera. The vanillyl group of RTX facilitates the action of the vanilloid receptor (VR-1), a non-selective cation channel expressed on suburothelial C-fibres. Intravesical therapy with a single dose of RTX results in early acute excitatory effects (“sensitisation”) followed by inhibition of neuropeptide release and neuronal terminal field degeneration (“desensitisation”) (Avelino et al., 2001). In patients with refractory NDO, it has been shown that intravesical therapy with vanilloid compounds such as RTX or capsaicin significantly decreases lower urinary tract symptoms for a period of weeks or months, depending on factors such as dose and disease progression. It is thought that the eventual recurrence of symptoms is related to C-fibre regeneration. We have previously shown that the mean suburothelial nerve density decreases in patients who respond to capsaicin. Our experimental aim is to measure suburothelial nerve density in flexible cystoscopic biopsies in controls and patients with NDO before and after intravesical RTX or placebo. -
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. -
The Role of Phytotoxic and Antimicrobial Compounds of Euphorbia Gummifera in the Cause and Maintenance of the Fairy Circles of Namibia
The role of phytotoxic and antimicrobial compounds of Euphorbia gummifera in the cause and maintenance of the fairy circles of Namibia by Nicole Galt Submitted in partial fulfillment of the requirements for the degree Magister Scientiae Department of Plant and Soil Sciences Faculty of Natural and Agricultural Sciences University of Pretoria Pretoria Supervisor: Prof. J.J.M. Meyer March 2018 i The role of phytotoxic and antimicrobial compounds of Euphorbia gummifera in the cause and maintenance of the fairy circles of Namibia by Nicole Galt Department of Plant and Soil Sciences Faculty of Natural and Agricultural Sciences University of Pretoria Pretoria Supervisor: Prof. J.J.M. Meyer Degree: MSc Medicinal Plant Science Abstract Fairy circles (FC) are unexplained botanical phenomena of the pro-Namib desert and parts of the West Coast of South Africa. They are defined as circular to oval shaped anomalies of varying sizes that are left bereft of vegetation. Even though there are several distinctly different hypotheses that have aimed to explain the origin of fairy circles, none have done so to satisfaction of the scientific community. The aim of this study was to determine if phytotoxic and antibacterial properties of a co-occurring Euphorbia species, E. gummifera plays a role in the creation of fairy circles. Representative soil samples (from inside-, outside fairy circles and underneath dead E. gummifera plants) and plant samples (aerial ii parts of E. gummifera and intact grasses, Stipagrostis uniplumis) were collected from the area. The collected samples were used for a several biological assays. A soil bed bio-assay was done using the three collected soil types. -
TRPV1 and Endocannabinoids: Emerging Molecular Signals That Modulate Mammalian Vision
Cells 2014, 3, 914-938; doi:10.3390/cells3030914 OPEN ACCESS cells ISSN 2073-4409 www.mdpi.com/journal/cells Review TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision 1,2,†, 1,2,† 1,† 1,2,3,4, Daniel A. Ryskamp *, Sarah Redmon , Andrew O. Jo and David Križaj * 1 Department of Ophthalmology & Visual Sciences, Moran Eye Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA; E-Mails: [email protected] (S.R.); [email protected] (A.O.J.) 2 Interdepartmental Program in Neuroscience, University of Utah School of Medicine, Salt Lake City, UT 84132, USA 3 Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, USA 4 Center for Translational Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA † Those authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: [email protected] (D.A.R.); [email protected] (D.K.); Tel.: +1-801-213-2777 (D.K.); Fax: +1-801-587-8314 (D.K.). Received: 1 July 2014; in revised form: 27 August 2014 / Accepted: 5 September 2014 / Published: 12 September 2014 Abstract: Transient Receptor Potential Vanilloid 1 (TRPV1) subunits form a polymodal cation channel responsive to capsaicin, heat, acidity and endogenous metabolites of polyunsaturated fatty acids. While originally reported to serve as a pain and heat detector in the peripheral nervous system, TRPV1 has been implicated in the modulation of blood flow and osmoregulation but also neurotransmission, postsynaptic neuronal excitability and synaptic plasticity within the central nervous system. -
Snapshot: Mammalian TRP Channels David E
SnapShot: Mammalian TRP Channels David E. Clapham HHMI, Children’s Hospital, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA TRP Activators Inhibitors Putative Interacting Proteins Proposed Functions Activation potentiated by PLC pathways Gd, La TRPC4, TRPC5, calmodulin, TRPC3, Homodimer is a purported stretch-sensitive ion channel; form C1 TRPP1, IP3Rs, caveolin-1, PMCA heteromeric ion channels with TRPC4 or TRPC5 in neurons -/- Pheromone receptor mechanism? Calmodulin, IP3R3, Enkurin, TRPC6 TRPC2 mice respond abnormally to urine-based olfactory C2 cues; pheromone sensing 2+ Diacylglycerol, [Ca ]I, activation potentiated BTP2, flufenamate, Gd, La TRPC1, calmodulin, PLCβ, PLCγ, IP3R, Potential role in vasoregulation and airway regulation C3 by PLC pathways RyR, SERCA, caveolin-1, αSNAP, NCX1 La (100 µM), calmidazolium, activation [Ca2+] , 2-APB, niflumic acid, TRPC1, TRPC5, calmodulin, PLCβ, TRPC4-/- mice have abnormalities in endothelial-based vessel C4 i potentiated by PLC pathways DIDS, La (mM) NHERF1, IP3R permeability La (100 µM), activation potentiated by PLC 2-APB, flufenamate, La (mM) TRPC1, TRPC4, calmodulin, PLCβ, No phenotype yet reported in TRPC5-/- mice; potentially C5 pathways, nitric oxide NHERF1/2, ZO-1, IP3R regulates growth cones and neurite extension 2+ Diacylglycerol, [Ca ]I, 20-HETE, activation 2-APB, amiloride, Cd, La, Gd Calmodulin, TRPC3, TRPC7, FKBP12 Missense mutation in human focal segmental glomerulo- C6 potentiated by PLC pathways sclerosis (FSGS); abnormal vasoregulation in TRPC6-/- -
Transient Receptor Potential Channels and Metabolism
Molecules and Cells Minireview Transient Receptor Potential Channels and Metabolism Subash Dhakal and Youngseok Lee* Department of Bio and Fermentation Convergence Technology, Kookmin University, BK21 PLUS Project, Seoul 02707, Korea *Correspondence: [email protected] https://doi.org/10.14348/molcells.2019.0007 www.molcells.org Transient receptor potential (TRP) channels are nonselective Montell, 2007). These cationic channels were first charac- cationic channels, conserved among flies to humans. Most terized in the vinegar fly, Drosophila melanogaster. While TRP channels have well known functions in chemosensation, a visual mechanism using forward genetic screening was thermosensation, and mechanosensation. In addition to being studied, a mutant fly showed a transient response to being sensing environmental changes, many TRP channels constant light instead of the continuous electroretinogram are also internal sensors that help maintain homeostasis. response recorded in the wild type (Cosens and Manning, Recent improvements to analytical methods for genomics 1969). Therefore, the mutant was named as transient recep- and metabolomics allow us to investigate these channels tor potential (trp). In the beginning, researchers had spent in both mutant animals and humans. In this review, we two decades discovering the trp locus with the germ-line discuss three aspects of TRP channels, which are their role transformation of the genomic region (Montell and Rubin, in metabolism, their functional characteristics, and their 1989). Using a detailed structural permeation property anal- role in metabolic syndrome. First, we introduce each TRP ysis in light-induced current, the TRP channel was confirmed channel superfamily and their particular roles in metabolism. as a six transmembrane domain protein, bearing a structural Second, we provide evidence for which metabolites TRP resemblance to a calcium-permeable cation channel (Mon- channels affect, such as lipids or glucose. -
Photoswitchable Fatty Acids Enable Optical Control of TRPV1
ARTICLE Received 18 Nov 2014 | Accepted 8 Apr 2015 | Published 22 May 2015 DOI: 10.1038/ncomms8118 OPEN Photoswitchable fatty acids enable optical control of TRPV1 James Allen Frank1, Mirko Moroni2, Rabih Moshourab2,3, Martin Sumser1, Gary R. Lewin2 & Dirk Trauner1 Fatty acids (FAs) are not only essential components of cellular energy storage and structure, but play crucial roles in signalling. Here we present a toolkit of photoswitchable FA analogues (FAAzos) that incorporate an azobenzene photoswitch along the FA chain. By modifying the FAAzos to resemble capsaicin, we prepare a series of photolipids targeting the Vanilloid Receptor 1 (TRPV1), a non-selective cation channel known for its role in nociception. Several azo-capsaicin derivatives (AzCAs) emerge as photoswitchable agonists of TRPV1 that are relatively inactive in the dark and become active on irradiation with ultraviolet-A light. This effect can be rapidly reversed by irradiation with blue light and permits the robust optical control of dorsal root ganglion neurons and C-fibre nociceptors with precision timing and kinetics not available with any other technique. More generally, we expect that photolipids will find many applications in controlling biological pathways that rely on protein–lipid interactions. 1 Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstrasse 5–13, Munich 81377, Germany. 2 Molecular Physiology of Somatic Sensation, Max Delbru¨ck Center for Molecular Medicine, Berlin 13125, Germany. 3 Department of Anesthesiology, Campus Charite´ Mitte und Virchow Klinikum, Charite´ Universita¨tsmedizin Berlin, Augustburgerplatz 1, Berlin 13353, Germany. Correspondence and requests for materials should be addressed to D.T.