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Nicotinic Stimulation Produces Multiple Forms of Increased Glutamatergic Synaptic Transmission
The Journal of Neuroscience, September 15, 1998, 18(18):7075–7083 Nicotinic Stimulation Produces Multiple Forms of Increased Glutamatergic Synaptic Transmission Kristofer A. Radcliffe and John A. Dani Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030-3498 Synaptic modulation and long-term synaptic changes are initiate calcium-dependent mechanisms that are known to in- thought to be the cellular correlates for learning and memory duce glutamatergic synaptic plasticity. The results with evoked (Madison et al., 1991; Aiba et al., 1994; Goda and Stevens, synaptic currents showed that nAChR activity can alter the 1996). The hippocampus is a center for learning and memory relationship between the incoming presynaptic activity and that receives abundant cholinergic innervation and has a high outgoing postsynaptic signaling along glutamatergic fibers. density of nicotinic acetylcholine receptors (nAChRs) (Wada et Thus, the same information arriving along the same glutama- al., 1989; Woolf, 1991). We report that strong, brief stimulation tergic afferents will be processed differently when properly of nAChRs enhanced hippocampal glutamatergic synaptic timed nicotinic activity converges onto the glutamatergic pre- transmission on two independent time scales and altered the synaptic terminals. Influencing information processing at gluta- relationship between consecutively evoked synaptic currents. matergic synapses may be one way in which nicotinic cholin- The nicotinic synaptic enhancement required extracellular cal- ergic activity influences cognitive processes. Disruption of cium and was produced by the activation of presynaptic a7- these nicotinic cholinergic mechanisms may contribute to the containing nAChRs. Although one form of glutamatergic en- deficits associated with the degeneration of cholinergic func- hancement lasted only for seconds, another form lasted for tions during Alzheimer’s disease. -
Neuronal Nicotinic Receptors: from Structure to Pathology
Progress in Neurobiology 74 (2004) 363–396 www.elsevier.com/locate/pneurobio Neuronal nicotinic receptors: from structure to pathology C. Gotti, F. Clementi* CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology Section, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy Received 22 July 2004; accepted 29 September 2004 Available online 27 October 2004 Abstract Neuronal nicotinic receptors (NAChRs) form a heterogeneous family of ion channels that are differently expressed in many regions of the central nervous system (CNS) and peripheral nervous system. These different receptor subtypes, which have characteristic pharmacological and biophysical properties, have a pentameric structure consisting of the homomeric or heteromeric combination of 12 different subunits (a2–a10, b2–b4). By responding to the endogenous neurotransmitter acetylcholine, NAChRs contribute to a wide range of brain activities and influence a number of physiological functions. Furthermore, it is becoming evident that the perturbation of cholinergic nicotinic neurotransmission can lead to various diseases involving nAChR dysfunction during development, adulthood and ageing. In recent years, it has been discovered that NAChRs are present in a number of non-neuronal cells where they play a significant functional role and are the pathogenetic targets in several diseases. NAChRs are also the target of natural ligands and toxins including nicotine (Nic), the most widespread drug of abuse. This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining their regional and cellular localisation and the molecular basis of their functional diversity mainly in pharmacological and biochemical terms. -
Prefrontal Α7nachr Signaling Differentially Modulates Afferent
Research Articles: Systems/Circuits Prefrontal α7nAChR signaling differentially modulates afferent drive and trace fear conditioning behavior in adolescent and adult rats https://doi.org/10.1523/JNEUROSCI.1941-20.2020 Cite as: J. Neurosci 2021; 10.1523/JNEUROSCI.1941-20.2020 Received: 27 July 2020 Revised: 29 November 2020 Accepted: 23 December 2020 This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data. Alerts: Sign up at www.jneurosci.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Copyright © 2021 the authors 1 Prefrontal α7nAChR signaling differentially modulates afferent drive 2 and trace fear conditioning behavior in adolescent and adult rats 3 4 5 6 7 Running title: Prefrontal α7nAChR control of afferent drive 8 9 10 11 Anabel M. M. Miguelez Fernandez, Hanna M. Molla, Daniel R. Thomases, and Kuei Y. Tseng* 12 13 Department of Anatomy and Cell Biology, University of Illinois at Chicago, IL 14 15 16 17 *Corresponding Author: Kuei Y. Tseng, MD, PhD 18 Department of Anatomy and Cell Biology 19 University of Illinois at Chicago – College of Medicine 20 Chicago, IL 60612, USA 21 Email: [email protected] 22 23 24 Number of figures: 8 25 Number of tables: 0 26 Abstract: 250 27 Main text: 4,030 words (Introduction: 451; Methods: 1,205; Results: 979; Discussion: 1,395) 28 29 30 31 32 Acknowledgements 33 Supported by NIH Grants R01-MH086507 and R01-MH105488 to KYT, and UIC College of Medicine 34 funds to KYT. -
Differing Time Dependencies of Object Recognition Memory Impairments Produced by Nicotinic and Muscarinic Cholinergic Antagonism in Perirhinal Cortex
Downloaded from learnmem.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Research Differing time dependencies of object recognition memory impairments produced by nicotinic and muscarinic cholinergic antagonism in perirhinal cortex Chris J. Tinsley,1,3 Nadine S. Fontaine-Palmer,1 Maria Vincent,1 Emma P.E. Endean,1 John P. Aggleton,2 Malcolm W. Brown,1 and E. Clea Warburton1 1MRC Centre for Synaptic Plasticity, School of Physiological Sciences, Bristol University, Bristol BS8 1TD, United Kingdom; 2School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom The roles of muscarinic and nicotinic cholinergic receptors in perirhinal cortex in object recognition memory were com- pared. Rats’ discrimination of a novel object preference test (NOP) test was measured after either systemic or local infusion into the perirhinal cortex of the nicotinic receptor antagonist methyllycaconitine (MLA), which targets alpha-7 (a7) amongst other nicotinic receptors or the muscarinic receptor antagonists scopolamine, AFDX-384, and pirenzepine. Methyllycaconitine administered systemically or intraperirhinally before acquisition impaired recognition memory tested after a 24-h, but not a 20-min delay. In contrast, all three muscarinic antagonists produced a similar, unusual pattern of impairment with amnesia after a 20-min delay, but remembrance after a 24-h delay. Thus, the amnesic effects of nicotinic and muscarinic antagonism were doubly dissociated across the 20-min and 24-h delays. The same pattern of shorter-term but not longer-term memory impairment was found for scopolamine whether the object preference test was carried out in a square arena or a Y-maze and whether rats of the Dark Agouti or Lister-hooded strains were used. -
Neuronal Nicotinic Receptors
NEURONAL NICOTINIC RECEPTORS Dr Christopher G V Sharples and preparations lend themselves to physiological and pharmacological investigations, and there followed a Professor Susan Wonnacott period of intense study of the properties of nAChR- mediating transmission at these sites. nAChRs at the Department of Biology and Biochemistry, muscle endplate and in sympathetic ganglia could be University of Bath, Bath BA2 7AY, UK distinguished by their respective preferences for C10 and C6 polymethylene bistrimethylammonium Susan Wonnacott is Professor of compounds, notably decamethonium and Neuroscience and Christopher Sharples is a hexamethonium,5 providing the first hint of diversity post-doctoral research officer within the among nAChRs. Department of Biology and Biochemistry at Biochemical approaches to elucidate the structure the University of Bath. Their research and function of the nAChR protein in the 1970’s were focuses on understanding the molecular and facilitated by the abundance of nicotinic synapses cellular events underlying the effects of akin to the muscle endplate, in electric organs of the acute and chronic nicotinic receptor electric ray,Torpedo , and eel, Electrophorus . High stimulation. This is with the goal of affinity snakea -toxins, principallyaa -bungarotoxin ( - Bgt), enabled the nAChR protein to be purified, and elucidating the structure, function and subsequently resolved into 4 different subunits regulation of neuronal nicotinic receptors. designateda ,bg , and d .6 An additional subunit, e , was subsequently identified in adult muscle. In the early 1980’s, these subunits were cloned and sequenced, The nicotinic acetylcholine receptor (nAChR) arguably and the era of the molecular analysis of the nAChR has the longest history of experimental study of any commenced. -
Nociceptive Thresholds Are Controlled Through Spinal ОІ2-Subunit
PAINÒ 152 (2011) 2131–2137 www.elsevier.com/locate/pain Nociceptive thresholds are controlled through spinal b2-subunit-containing nicotinic acetylcholine receptors Ipek Yalcin a, Alexandre Charlet a,b, Matilde Cordero-Erausquin a, Luc-Henri Tessier a, Marina R. Picciotto c, ⇑ Rémy Schlichter a,b, Pierrick Poisbeau a,b, Marie-José Freund-Mercier a,b, Michel Barrot a, a Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France b Faculté des Sciences de la Vie, Université de Strasbourg, Strasbourg, France c Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. article info abstract Article history: Although cholinergic drugs are known to modulate nociception, the role of endogenous acetylcholine in Received 13 October 2010 nociceptive processing remains unclear. In the current study, we evaluated the role of cholinergic trans- Received in revised form 8 April 2011 mission through spinal b2-subunit-containing nicotinic acetylcholine receptors in the control of nocicep- Accepted 8 May 2011 tive thresholds. We show that mechanical and thermal nociceptive thresholds are significantly lowered ⁄ ⁄ in b2 -knockout (KO) mice. Using nicotinic antagonists in these mice, we demonstrate that b2 -nAChRs are responsible for tonic inhibitory control of mechanical thresholds at the spinal level. We further Keywords: hypothesized that tonic b ⁄-nAChR control of mechanical nociceptive thresholds might implicate GAB- Nicotinic 2 Aergic transmission since spinal nAChR stimulation can enhance inhibitory transmission. Indeed, the b -nAChRs 2 ⁄ Acetylcholine GABAA receptor antagonist bicuculline decreased the mechanical threshold in wild-type but not b2 -KO ⁄ ⁄ GABA mice, and the agonist muscimol restored basal mechanical threshold in b2 -KO mice. -
Muscle Relaxants
Muscle relaxants ●cause relaxation of striated (voluntary skeletal) musculature (in contrast to spasmolytics which relax unstriped musculature) Classification of myorelaxants 1. Neuromuscular blocking drugs ●periferial (direct) myorelaxants: interact with acetylcholine nicotinic (N) receptors of skeletal musculature a) stabilizing myorelaxants – N-receptors antagonists b) depolarizing myorelaxants – N-receptors agonists ●continuous N-receptors stimulation depolarization of cells functional antagonism: further leading of impulses imposible, no muscle contraction c) indirect myorelaxants: botulinum toxin ●irreversibly inhibits acetycholine releasing 2. Central muscle relaxants ●acts in CNS ●structurally heterogenic group ●compounds with various mechanisms of action Stabilizing myorelaxants ●N-receptors antagonists in skeletal muscle cells ●usage: surgical operative measures (often as a part of some form of anaesthesia) ●structures derived from curare alkaloids Curare: arrow poison of South American Indians ●preparation from various plants ●contained a complex mixture of alkaloids Curare classification: according to preparation and package in which it was shipped to Europe 1. Tubocurare: in hollow bamboo rods 2. Calebase curare: in bottle-shaped cucurbits (gourds, calabashes - from plants of genus Strychnos) 3. Pot curare: in ceramic vessels Structural types: 1. Benzyltetrahydroisoquinolines: tubocurarine (from tubocurare) atracurium besylate (synthetic) mivacurium besylate (synthetic) etc. 2. Indole derivatives: toxiferine C alcuronium chloride 3. Steroids with basic substituents: vecuronium bromide pancuronium bromide rocuronium bromide 1. Benzyltetrahydroisoquinolines H3C O H C O O CH3 3 H3C H + H3C H C O O H3C N O 3 OH H C 3 O O H3C H H H + CH + N 3 O O N OH O CH3 N CH3 O O O H3C O CH3 O CH3 tubocurarine atracurium ●used as besylate Tracrium ® inj. -
Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders
Brain Sci. 2015, 5, 258-274; doi:10.3390/brainsci5030258 OPEN ACCESS brain sciences ISSN 2076-3425 www.mdpi.com/journal/brainsci/ Review Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders Joan Y. Holgate * and Selena E. Bartlett Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, 37 Kent St, Woolloongabba, Queensland 4102, Australia; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +61-7-3443-7285; Fax: +61-7-3443-7779. Academic Editor: Marcelo Febo Received: 15 April 2015 / Accepted: 18 June 2015 / Published: 30 June 2015 Abstract: Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. -
The Pharmacologist 2 0 0 8 March
Vol. 50 Number 1 The Pharmacologist 2 0 0 8 March Happy Birthday ASPET!!! th 100 Anniversary Celebration Details Inside: Don’t Miss the ASPET Centennial Meeting At Experimental Biology 2008 April 5-9, 2008, San Diego Featuring: Exciting Opening Reception: DJ, Food, Drinks and more Special Centennial Symposia: Exciting topics from each division Centennial Store: Selling ASPET merchandise for the first time ever ASPET Birthday Party: A Street Festival in the Gaslamp District ASPET Student Fiesta: Band, Food, and Drinks Nobel Laureate Reception: For Students to meet Nobel Laureates Great Giveaways: Luggage Tags, Pins, Posters, Compendiums Abel Number Lounge: Look up your Abel Number Plus Much More!! Also Inside this Issue: ASPET Election Results ASPET Award Winners 2008 EB 2008 Program Grid Special Executive Officer Interview Abstracts from the Great Lakes Chapter and Southeastern Chapter Meetings A Publication of the American Society for 1 Pharmacology and Experimental Therapeutics - ASPET Volume 50 Number 1, 2008 The Pharmacologist is published and distributed by the American Society for Pharmacology and Experimental Therapeutics. The PHARMACOLOGIST Editor Suzie Thompson EDITORIAL ADVISORY BOARD News Bryan F. Cox, Ph.D. Ronald N. Hines, Ph.D. Terrence J. Monks, Ph.D. Election Results . page 3 COUNCIL Award Winners for 2008. page 4 President Kenneth P. Minneman, Ph.D. EB 2008 Program Grid . page 12 President-Elect ASPET Centennial Update . page 17 Joe A. Beavo, Ph.D. Past President Special Centennial Feature: The View From the Elaine Sanders-Bush, Ph.D. Executive Office . page 21 Secretary/Treasurer Annette E. Fleckenstein, Ph.D. Special Lecture: The Origin and Development of Secretary/Treasurer-Elect Behavioral Pharmacology . -
Two Distinct Nicotinic Receptors, One Pharmacologically Similar to the Vertebrate ␣7-Containing Receptor, Mediate Cl Currents in Aplysia Neurons
The Journal of Neuroscience, October 15, 1998, 18(20):8198–8213 Two Distinct Nicotinic Receptors, One Pharmacologically Similar to the Vertebrate a7-Containing Receptor, Mediate Cl Currents in Aplysia Neurons JacSue Kehoe1 and J. Michael McIntosh2 1Laboratoire de Neurobiologie, Ecole Normale Supe´ rieure, Paris 75005, France, and 2Departments of Psychiatry and Biology, University of Utah, Salt Lake City, Utah 84112 Ionotropic, nicotinic receptors have previously been shown to toxin; the other is a slowly desensitizing current that is unaf- mediate both inhibitory (Cl-dependent) and excitatory (cationic) fected by the toxin. The two kinetically defined elements were cholinergic responses in Aplysia neurons. We have used fast also found to be differentially sensitive to different agonists. perfusion methods of agonist and antagonist application to Finally, the proportion of the rapidly desensitizing element to reevaluate the effects on these receptors of a wide variety of the sustained element was found to be cell-specific. These cholinergic compounds, including a number of recently isolated observations led to the conclusion that two distinct nicotinic and/or synthesized a toxins [a-conotoxin (aCTx)] from Conus receptors mediate Cl currents in Aplysia neurons. The receptor snails. These toxins have been shown in previous studies to mediating the rapidly desensitizing Cl-dependent response discriminate between the many types of nicotinic receptors shows a strong pharmacological resemblance to the vertebrate now known to be expressed in vertebrate muscle, neuroendo- a-bungarotoxin-sensitive, a7-containing receptor, which is per- crine, and neuronal cells. One of these toxins (aCTx ImI from meable to calcium and mediates a rapidly desensitizing exci- the worm-eating snail Conus imperialis) revealed that two ki- tatory response. -
Modes of Action of Herbal Medicines and Plant Secondary Metabolites
Medicines 2015, 2, 251-286; doi:10.3390/medicines2030251 OPEN ACCESS medicines ISSN 2305-6320 www.mdpi.com/journal/medicines Review Modes of Action of Herbal Medicines and Plant Secondary Metabolites Michael Wink Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, Heidelberg D-69120, Germany; E-Mail: [email protected]; Tel.: +49-6221-544-881; Fax: +49-6221-544-884 Academic Editor: Shufeng Zhou Received: 13 August 2015 / Accepted: 31 August 2015 / Published: 8 September 2015 Abstract: Plants produce a wide diversity of secondary metabolites (SM) which serve them as defense compounds against herbivores, and other plants and microbes, but also as signal compounds. In general, SM exhibit a wide array of biological and pharmacological properties. Because of this, some plants or products isolated from them have been and are still used to treat infections, health disorders or diseases. This review provides evidence that many SM have a broad spectrum of bioactivities. They often interact with the main targets in cells, such as proteins, biomembranes or nucleic acids. Whereas some SM appear to have been optimized on a few molecular targets, such as alkaloids on receptors of neurotransmitters, others (such as phenolics and terpenoids) are less specific and attack a multitude of proteins by building hydrogen, hydrophobic and ionic bonds, thus modulating their 3D structures and in consequence their bioactivities. The main modes of action are described for the major groups of common plant secondary metabolites. The multitarget activities of many SM can explain the medical application of complex extracts from medicinal plants for more health disorders which involve several targets. -
PDF Hosted at the Radboud Repository of the Radboud University Nijmegen
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Radboud Repository PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/24502 Please be advised that this information was generated on 2017-12-05 and may be subject to change. Neuromuscular transmission and its pharmacological blockade Part 1: Neuromuscular transmission and general aspects of its blockade • Leo H. D. J. Boolj 1.1 .Introduction Muscle relaxation is an important tool in the treat ment of patients during anaesthesia for surgical and diagnostics procedures, and during treatment in the intensive care unit. Such muscle relaxation is obtained by pharmacological intervention with neuromuscular transmission with either depolarizing or non-depolar- izing relaxants. Suxamethonium presently is the only depolarizer in clinical use, but has many adverse effects. A large number of non-depolarizing relaxants has been introduced into clinical practice; however, none of them matches perfectly with the 'ideal mus cle relaxant7. This demands the development of new compounds. Some of the new development in neuro muscular transmission and its blockers are discussed. 1.2.Neuromuscular transmission For normal muscular functions an impulse must be transferred from the nerve terminal to the muscle. Such a transfer takes place at the neuromuscular junc tion, which consist of the nerve terminal, a 50-100 nm wide junctional cleft, and the postjunctional mus cle membrane [1], Booij LHDJ. Neuromuscular transmission and its pharmacologi - In research on the neuromuscular junction it has cal blockade.