G Protein‐Coupled Receptors

Total Page:16

File Type:pdf, Size:1020Kb

G Protein‐Coupled Receptors S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology (2019) 176, S21–S141 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors Stephen PH Alexander1 , Arthur Christopoulos2 , Anthony P Davenport3 , Eamonn Kelly4, Alistair Mathie5 , John A Peters6 , Emma L Veale5 ,JaneFArmstrong7 , Elena Faccenda7 ,SimonDHarding7 ,AdamJPawson7 , Joanna L Sharman7 , Christopher Southan7 , Jamie A Davies7 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia 3Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK 4School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 5Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 6Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 7Centre for Discovery Brain Sciences, 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. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion chan- nels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate. Conflict of interest The authors state that there are no conflicts of interest to disclose. © 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Overview: G protein-coupled receptors (GPCRs) are the largest class of membrane proteins in the human genome. The term "7TM receptor" is commonly used interchangeably with "GPCR", although there are some receptors with seven transmembrane domains that do not signal through G proteins. GPCRs share a common architecture, each consisting of a single polypeptide with an extracellular N-terminus, an intracellular C-terminus and seven hydrophobic transmembrane domains (TM1-TM7) linked by three extracellular loops (ECL1-ECL3) and three intracellular loops (ICL1-ICL3). About 800 GPCRs have been identified in man, of which about half have sensory functions, mediating olfaction (˜400), taste (33), light perception (10) and pheromone signalling (5) [1479]. The remaining 350 non-sensory GPCRs mediate signalling by ligands that range in size from small molecules to peptides to large proteins; they are the targets for the majority of drugs in clinical usage [1642, 1772], although only a minority of these receptors are exploited therapeutically. The first classification scheme to be proposed for GPCRs [1129] divided them, on the basic of sequence homology, into six classes. These Searchable database: http://www.guidetopharmacology.org/index.jsp G protein-coupled receptors S21 Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14748/full S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology (2019) 176, S21–S141 classes and their prototype members were as follows: Class A (rhodopsin-like), Class B (secretin receptor family), Class C (metabotropic glutamate), Class D (fungal mating pheromone receptors), Class E (cyclic AMP receptors) and Class F (frizzled/smoothened). Of these, classes D and E are not found in vertebrates. An alternative classification scheme "GRAFS" [1890] divides vertebrate GPCRs into five classes, overlapping with the A-F nomenclature, viz: Glutamate family (class C), which includes metabotropic glutamate receptors, a calcium-sensing receptor and GABAB receptors, as well as three taste type 1 receptors and a family of pheromone receptors (V2 receptors) that are abundant in rodents but absent in man [1479]. Rhodopsin family (class A), which includes receptors for a wide variety of small molecules, neurotransmitters, peptides and hormones, together with olfactory receptors, visual pigments, taste type 2 receptors and five pheromone receptors (V1 receptors). Adhesion family GPCRs are phylogenetically related to class B receptors, from which they differ by possessing large extracellular N-termini that are autoproteolytically cleaved from their 7TM domains at a conserved "GPCR proteolysis site" (GPS) which lies within a much larger (320 residue) "GPCR autoproteolysis-inducing" (GAIN) domain, an evolutionary ancient mofif also found in polycystic kidney disease 1 (PKD1)-like proteins, which has been suggested to be both required and sufficient for autoproteolysis [1743]. Frizzled family consists of 10 Frizzled proteins (FZD(1-10)) and Smoothened (SMO). The FZDs are activated by secreted lipoglycoproteins of the WNT family, whereas SMO is indirectly activated by the Hedgehog (HH) family of proteins acting on the transmembrane protein Patched (PTCH). Secretin family, encoded by 15 genes in humans. The ligands for receptors in this family are polypeptide hormones of 27-141 amino acid residues; nine of the mammalian receptors respond to ligands that are structurally related to one another (glucagon, glucagon-like peptides (GLP-1, GLP-2), glucose-dependent insulinotropic polypeptide (GIP), secretin, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP) and growth-hormone-releasing hormone (GHRH)) [811]. GPCR families Family Class A Class B (Secretin) Class C (Glutamate) Adhesion Frizzled Receptors with known ligands 197 15 12 0 11 Orphans 87 (54)a - 8 (1)a 26 (6)a 0 Sensory (olfaction) 390b,c -- -- Sensory (vision) 10d opsins - - - - Sensory (taste) 30c taste 2 - 3c taste 1 - - Sensory (pheromone) 5c vomeronasal 1 - - - - Total 719 15 22 33 11 aNumbers in brackets refer to orphan receptors for which an endogenous ligand has been proposed in at least one publication, see [455]; b[1634]; c[1479]; d[2109]. β Much of our current understanding of the structure and function of GPCRs is the result of pioneering work on the visual pigment rhodopsin and on the 2 adrenoceptor, the latter culminating in the award of the 2012 Nobel Prize in chemistry to Robert Lefkowitz and Brian Kobilka [1121, 1244]. Pseudogenes Below is a curated list of pseudogenes that in humans are non-coding for receptor protein. In some cases these have a shared ancestry with genes that encode functional receptors in rats and mice. ADGRE4P, GNRHR2, GPR79, HTR5BP, NPY6R, TAAR3P, TAAR4P, TAAR7P, TAS2R12P, TAS2R15P, TAS2R18P, TAS2R2P, TAS2R62P, TAS2R63P, TAS2R64P, TAS2R67P, TAS2R68P, TAS2R6P. A more detailed listing containg further information can be viewed here. Olfactory receptors Olfactory receptors are also seven-transmembrane spanning G protein-coupled receptors, responsible for the detection of odorants. These are not currently included as they are not yet associated with extensive pharmacological data but are curated in the following databases: The gene list of olfactory receptors at HGNC, and curated by HORDE and ORDB. Searchable database: http://www.guidetopharmacology.org/index.jsp G protein-coupled receptors S22 Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.14748/full S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology (2019) 176, S21–S141 Further reading on G protein-coupled receptors Kenakin T. (2018) Is the Quest for Signaling Bias Worth the Effort? Mol. Pharmacol. 93: 266-269 Roth BL et al. (2017) Discovery of new GPCR ligands to illuminate new biology. Nat. Chem. Biol. 13: [PMID:29348268] 1143-1151 [PMID:29045379] Michel MC et al. (2018) Biased Agonism in Drug Discovery-Is It Too Soon to Choose a Path? Mol.
Recommended publications
  • Strategies to Increase ß-Cell Mass Expansion
    This electronic thesis or dissertation has been downloaded from the King’s Research Portal at https://kclpure.kcl.ac.uk/portal/ Strategies to increase -cell mass expansion Drynda, Robert Lech Awarding institution: King's College London The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without proper acknowledgement. END USER LICENCE AGREEMENT Unless another licence is stated on the immediately following page this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence. https://creativecommons.org/licenses/by-nc-nd/4.0/ You are free to copy, distribute and transmit the work Under the following conditions: Attribution: You must attribute the work in the manner specified by the author (but not in any way that suggests that they endorse you or your use of the work). Non Commercial: You may not use this work for commercial purposes. No Derivative Works - You may not alter, transform, or build upon this work. Any of these conditions can be waived if you receive permission from the author. Your fair dealings and other rights are in no way affected by the above. Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 Strategies to increase β-cell mass expansion A thesis submitted by Robert Drynda For the degree of Doctor of Philosophy from King’s College London Diabetes Research Group Division of Diabetes & Nutritional Sciences Faculty of Life Sciences & Medicine King’s College London 2017 Table of contents Table of contents .................................................................................................
    [Show full text]
  • The Activation of the Glucagon-Like Peptide-1 (GLP-1) Receptor by Peptide and Non-Peptide Ligands
    The Activation of the Glucagon-Like Peptide-1 (GLP-1) Receptor by Peptide and Non-Peptide Ligands Clare Louise Wishart Submitted in accordance with the requirements for the degree of Doctor of Philosophy of Science University of Leeds School of Biomedical Sciences Faculty of Biological Sciences September 2013 I Intellectual Property and Publication Statements The candidate confirms that the work submitted is her own and that appropriate credit has been given where reference has been made to the work of others. This copy has been supplied on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. The right of Clare Louise Wishart to be identified as Author of this work has been asserted by her in accordance with the Copyright, Designs and Patents Act 1988. © 2013 The University of Leeds and Clare Louise Wishart. II Acknowledgments Firstly I would like to offer my sincerest thanks and gratitude to my supervisor, Dr. Dan Donnelly, who has been nothing but encouraging and engaging from day one. I have thoroughly enjoyed every moment of working alongside him and learning from his guidance and wisdom. My thanks go to my academic assessor Professor Paul Milner whom I have known for several years, and during my time at the University of Leeds he has offered me invaluable advice and inspiration. Additionally I would like to thank my academic project advisor Dr. Michael Harrison for his friendship, help and advice. I would like to thank Dr. Rosalind Mann and Dr. Elsayed Nasr for welcoming me into the lab as a new PhD student and sharing their experimental techniques with me, these techniques have helped me no end in my time as a research student.
    [Show full text]
  • Behavioral Evidence for A-Opioid and 5-HT 2A Receptor Interactions
    European Journal of Pharmacology 474 (2003) 77–83 www.elsevier.com/locate/ejphar Behavioral evidence for A-opioid and 5-HT2A receptor interactions Gerard J. Marek* Department of Psychiatry, Yale School of Medicine, New Haven, CT 06508, USA Received 13 February 2003; received in revised form 3 June 2003; accepted 11 June 2003 Abstract Electrophysiological studies have demonstrated a physiological interaction between 5-HT2A and A-opioid receptors in the medial prefrontal cortex. Furthermore, behavioral studies have found that phenethylamine hallucinogens induce head shakes when directly administered into the medial prefrontal cortex. The receptor(s) by which morphine suppresses head shakes induced by serotonin agonists have not been characterized. We administered A-opioid receptor agonists and antagonists to adult male Sprague–Dawley rats prior to treatment with the phenethylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which is known to induce head shakes via 5-HT2A receptors. The suppressant action of the moderately selective A-opioid receptor agonist, buprenorphine (ID50f0.005 mg/ kg, i.p.; a A-opioid receptor partial agonist and n-opioid receptor antagonist) was blocked by naloxone and pretreatment with the irreversible A-opioid receptor antagonist clocinnamox. Another A-opioid receptor agonist fentanyl also suppressed DOI-induced head shakes. In contrast, a y-opioid receptor agonist was without effect on DOI-induced head shakes. Thus, activation of A-opioid receptors can suppress head shakes induced by hallucinogenic drugs. D 2003 Elsevier B.V. All rights reserved. Keywords: Phenethylamine; Hallucinogen; 5-HT (5-hydroxytryptamine, serotonin); A-Opioid receptor; Head shake; DOI; 5-HT2A receptor; Buprenorphine; Fentanyl 1.
    [Show full text]
  • Modulation by Trace Amine-Associated Receptor 1 of Experimental Parkinsonism, L-DOPA Responsivity, and Glutamatergic Neurotransmission
    The Journal of Neuroscience, October 14, 2015 • 35(41):14057–14069 • 14057 Neurobiology of Disease Modulation by Trace Amine-Associated Receptor 1 of Experimental Parkinsonism, L-DOPA Responsivity, and Glutamatergic Neurotransmission Alexandra Alvarsson,1* Xiaoqun Zhang,1* Tiberiu L Stan,1 Nicoletta Schintu,1 Banafsheh Kadkhodaei,2 Mark J. Millan,3 Thomas Perlmann,2,4 and Per Svenningsson1 1Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, SE-17176 Stockholm, Sweden, 2Ludwig Institute for Cancer Research, SE-17177 Stockholm, Sweden, 3Pole of Innovation in Neuropsychiatry, Institut de Recherches Servier, Centre de Recherches de Croissy, Paris 87290, France, and 4Department of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden Parkinson’s disease (PD) is a movement disorder characterized by a progressive loss of nigrostriatal dopaminergic neurons. Restoration of dopamine transmission by L-DOPA relieves symptoms of PD but causes dyskinesia. Trace Amine-Associated Receptor 1 (TAAR1) modulates dopaminergic transmission, but its role in experimental Parkinsonism and L-DOPA responses has been neglected. Here, we report that TAAR1 knock-out (KO) mice show a reduced loss of dopaminergic markers in response to intrastriatal 6-OHDA administra- tion compared with wild-type (WT) littermates. In contrast, the TAAR1 agonist RO5166017 aggravated degeneration induced by intra- striatal6-OHDAinWTmice.Subchronic L-DOPAtreatmentofTAAR1KOmiceunilaterallylesionedwith6-OHDAinthemedialforebrain bundle resulted in more pronounced rotational behavior and dyskinesia than in their WT counterparts. The enhanced behavioral sensitization to L-DOPA in TAAR1 KO mice was paralleled by increased phosphorylation of striatal GluA1 subunits of AMPA receptors. Conversely, RO5166017 counteracted both L-DOPA-induced rotation and dyskinesia as well as AMPA receptor phosphorylation.
    [Show full text]
  • Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System
    International Journal of Molecular Sciences Review Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System Shenglong Zou and Ujendra Kumar * Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-604-827-3660; Fax: +1-604-822-3035 Received: 9 February 2018; Accepted: 11 March 2018; Published: 13 March 2018 Abstract: The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids. Keywords: cannabinoid; endocannabinoid; receptor; signaling; central nervous system 1. Introduction The plant Cannabis sativa, better known as marijuana, has long been used for medical purpose throughout human history.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • The Impact of the Nonpeptide Corticotropin-Releasing Hormone Antagonist Antalarmin on Behavioral and Endocrine Responses to Stress*
    0013-7227/99/$03.00/0 Vol. 140, No. 1 Endocrinology Printed in U.S.A. Copyright © 1999 by The Endocrine Society The Impact of the Nonpeptide Corticotropin-Releasing Hormone Antagonist Antalarmin on Behavioral and Endocrine Responses to Stress* TERRENCE DEAK, KIEN T. NGUYEN, ANDREA L. EHRLICH, LINDA R. WATKINS, ROBERT L. SPENCER, STEVEN F. MAIER, JULIO LICINIO, MA-LI WONG, GEORGE P. CHROUSOS, ELIZABETH WEBSTER, AND PHILIP W. GOLD Department of Psychology (T.D., K.T.N., A.L.E., L.R.W., R.L.S., S.F.M.), University of Colorado, Boulder, Colorado 80309-0345; Clinical Neuroendocrinology Branch (J.L., M.-L.W., P.W.G.), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1284; and Developmental Neuroendocrinology Branch (G.P.C., E.W.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1284 ABSTRACT Furthermore, because rats previously exposed to inescapable shock The nonpeptide CRH antagonist antalarmin has been shown to (IS; 100 shocks, 1.6 mA, 5 sec each), demonstrate enhanced fear block both behavioral and endocrine responses to CRH. However, it’s conditioning, we investigated whether this effect would be blocked by potential activity in blunting behavioral and endocrine sequelae of antalarmin. Antalarmin (20 mg/kgz2 ml ip) impaired both the induc- stressor exposure has not been assessed. Because antagonism of cen- tion and expression of conditioned fear. In addition, antalarmin tral CRH by a-helical CRH attenuates conditioned fear responses, we blocked the enhancement of fear conditioning produced by prior ex- sought to test antalarmin in this regard.
    [Show full text]
  • Transcriptomic Analysis of Native Versus Cultured Human and Mouse Dorsal Root Ganglia Focused on Pharmacological Targets Short
    bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Transcriptomic analysis of native versus cultured human and mouse dorsal root ganglia focused on pharmacological targets Short title: Comparative transcriptomics of acutely dissected versus cultured DRGs Andi Wangzhou1, Lisa A. McIlvried2, Candler Paige1, Paulino Barragan-Iglesias1, Carolyn A. Guzman1, Gregory Dussor1, Pradipta R. Ray1,#, Robert W. Gereau IV2, # and Theodore J. Price1, # 1The University of Texas at Dallas, School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, 800 W Campbell Rd. Richardson, TX, 75080, USA 2Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine # corresponding authors [email protected], [email protected] and [email protected] Funding: NIH grants T32DA007261 (LM); NS065926 and NS102161 (TJP); NS106953 and NS042595 (RWG). The authors declare no conflicts of interest Author Contributions Conceived of the Project: PRR, RWG IV and TJP Performed Experiments: AW, LAM, CP, PB-I Supervised Experiments: GD, RWG IV, TJP Analyzed Data: AW, LAM, CP, CAG, PRR Supervised Bioinformatics Analysis: PRR Drew Figures: AW, PRR Wrote and Edited Manuscript: AW, LAM, CP, GD, PRR, RWG IV, TJP All authors approved the final version of the manuscript. 1 bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Adverse Effects of Stress on Drug Addiction
    Making a bad thing worse: adverse effects of stress on drug addiction Jessica N. Cleck, Julie A. Blendy J Clin Invest. 2008;118(2):454-461. https://doi.org/10.1172/JCI33946. Review Series Sustained exposure to various psychological stressors can exacerbate neuropsychiatric disorders, including drug addiction. Addiction is a chronic brain disease in which individuals cannot control their need for drugs, despite negative health and social consequences. The brains of addicted individuals are altered and respond very differently to stress than those of individuals who are not addicted. In this Review, we highlight some of the common effects of stress and drugs of abuse throughout the addiction cycle. We also discuss both animal and human studies that suggest treating the stress- related aspects of drug addiction is likely to be an important contributing factor to a long-lasting recovery from this disorder. Find the latest version: https://jci.me/33946/pdf Review series Making a bad thing worse: adverse effects of stress on drug addiction Jessica N. Cleck and Julie A. Blendy Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. Sustained exposure to various psychological stressors can exacerbate neuropsychiatric disorders, including drug addiction. Addiction is a chronic brain disease in which individuals cannot control their need for drugs, despite negative health and social consequences. The brains of addicted individuals are altered and respond very differently to stress than those of individuals who are not addicted. In this Review, we highlight some of the common effects of stress and drugs of abuse throughout the addiction cycle.
    [Show full text]
  • Celsr1-3 Cadherins in PCP and Brain Development
    CHAPTER SEVEN Celsr1–3 Cadherins in PCP and Brain Development Camille Boutin, André M. Goffinet1, Fadel Tissir1 Institute of Neuroscience, Developmental Neurobiology, Universite´ Catholique de Louvain, Brussels, Belgium 1Corresponding authors: Equal contribution. e-mail address: [email protected]; andre. [email protected] Contents 1. Celsr1–3 Expression Patterns 164 2. Celsr1: A Major Player in Vertebrate PCP 165 3. Celsr2 and 3 in Ciliogenesis 169 4. Celsr1–3 in Neuronal Migration 171 5. Celsr2 and Celsr3 in Brain Wiring 174 5.1 Motifs of Celsr important for their functions 176 References 179 Abstract Cadherin EGF LAG seven-pass G-type receptors 1, 2, and 3 (Celsr1–3) form a family of three atypical cadherins with multiple functions in epithelia and in the nervous system. During the past decade, evidence has accumulated for important and distinct roles of Celsr1–3 in planar cell polarity (PCP) and brain development and maintenance. Although the role of Celsr in PCP is conserved from flies to mammals, other functions may be more distantly related, with Celsr working only with one or a subset of the classical PCP partners. Here, we review the literature on Celsr in PCP and neural devel- opment, point to several remaining questions, and consider future challenges and possible research trends. Celsr1–3 genes encode atypical cadherins of more than 3000 amino acids ( Fig. 7.1). Their large ectodomain is composed of nine N-terminal cadherin repeats (typical cadherins have five repeats), six epidermal growth factor (EGF)-like domains, two laminin G repeats, one hormone receptor motif (HRM), and a G-protein-coupled receptor proteolytic site (GPS).
    [Show full text]
  • WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 36/84 (2006.01) A61K 31/5513 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/045 (2006.01) A61P 31/22 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/522 (2006.01) A61K 45/06 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/NL20 14/050780 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 13 November 2014 (13.1 1.2014) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/903,430 13 November 2013 (13. 11.2013) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: RJG DEVELOPMENTS B.V.
    [Show full text]
  • In the IUPHAR/BPS Guide to Pharmacology Database
    IUPHAR/BPS Guide to Pharmacology CITE https://doi.org/10.2218/gtopdb/F16/2019.4 Class A Orphans (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database Stephen P.H. Alexander1, Jim Battey2, Helen E. Benson3, Richard V. Benya4, Tom I. Bonner5, Anthony P. Davenport6, Satoru Eguchi7, Anthony Harmar3, Nick Holliday1, Robert T. Jensen2, Sadashiva Karnik8, Evi Kostenis9, Wen Chiy Liew3, Amy E. Monaghan3, Chido Mpamhanga10, Richard Neubig11, Adam J. Pawson3, Jean-Philippe Pin12, Joanna L. Sharman3, Michael Spedding13, Eliot Spindel14, Leigh Stoddart15, Laura Storjohann16, Walter G. Thomas17, Kalyan Tirupula8 and Patrick Vanderheyden18 1. University of Nottingham, UK 2. National Institutes of Health, USA 3. University of Edinburgh, UK 4. University of Illinois at Chicago, USA 5. National Institute of Mental Health, USA 6. University of Cambridge, UK 7. Temple University, USA 8. Cleveland Clinic Lerner Research Institute, USA 9. University of Bonn, Germany 10. LifeArc, UK 11. Michigan State University, USA 12. Université de Montpellier, France 13. Spedding Research Solutions SARL, France 14. Oregon Health & Science University, USA 15. University of Glasgow, UK 16. University of Utah, USA 17. University of Queensland, Australia 18. Vrije Universiteit Brussel, Belgium Abstract Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [191], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [148]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.
    [Show full text]