Central Functions of the Ghrelin Receptor PDF
Preview Central Functions of the Ghrelin Receptor
The Receptors Jeanelle Portelli Ilse Smolders Editors Central Functions of the Ghrelin Receptor The Receptors Volume 25 Series editor Giuseppe di Giovanni For furthervolumes: http://www.springer.com/series/7668 Jeanelle Portelli Ilse Smolders • Editors Central Functions of the Ghrelin Receptor Editors Jeanelle Portelli Ilse Smolders Department of PharmaceuticalChemistry Department of PharmaceuticalChemistry Center forNeurosciences, DrugAnalysis Center forNeurosciences, DrugAnalysis andDrugInformation andDrugInformation Vrije Universiteit Brussel Vrije Universiteit Brussel Brussels Brussels Belgium Belgium and Laboratory forClinical andExperimental Neurophysiology,Neurobiology and Neuropsychology Department of Neurology InstituteforNeuroscience Ghent UniversityHospital Gent Belgium ISBN 978-1-4939-0822-6 ISBN 978-1-4939-0823-3 (eBook) DOI 10.1007/978-1-4939-0823-3 Springer New YorkHeidelberg Dordrecht London LibraryofCongressControlNumber:2014937692 (cid:2)SpringerScience+BusinessMediaNewYork2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purposeofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthe work. Duplication of this publication or parts thereof is permitted only under the provisions of theCopyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the CopyrightClearanceCenter.ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper HumanaPressisabrandofSpringer SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Foreword It is my great pleasure and honor to write the Preface of this book dedicated to Ghrelin. FifteenyearshavepastsincethediscoveryofGhrelin.Duringtheseyearsalot of research has been done to elucidate the physiological functions of Ghrelin, not only a mere growth-hormone-releasing hormone, but also an important appetite regulator, energy conservator, and sympathetic nerve suppressor. At present, Ghrelin is the only circulating orexigenic hormone secreted from a peripheral organ and that acts on the hypothalamic arcuate nucleus, the regulatory region of appetite. AlthoughthediscoveryofGhrelinisdatedin1999,ithasalongerhistorysince Dr.Bowersdiscoveredthefirstgrowthhormonesecretagoguein1976,pavingthe way to identify the growth hormone secretagogue receptor, which was the key strategic protein for the discovery of Ghrelin. IrememberverywellthedaythatwebeganthesearchforGhrelin.ItwasApril 7,1998.ThatnightIfoundapaperinScience,whichreportedtheidentificationof the growth hormone secretagogue receptor. I had previously read the manuscript when it was published in the Science journal edition of August 1996. My first impression of the manuscript was why did the prestigious journal Science decide topublishthecloningofagrowthhormonereleasingpeptidereceptor.Iremember feeling confused with the fact that the cloning of the growth hormone releasing peptidereceptor,thatisthereceptorforanothergrowthhormonereleasingpeptide fromhypothalamus,hadbeenalreadypublished.Ireadthepaperaboutthegrowth hormone secretagogue receptor very carefully and had confidence that this receptor was a very good target to search for its endogenous ligand. TherehavebeenatleastfivemajorbreakthroughsinGhrelinresearch.Thefirst breakthrough, of course, is the discovery of growth hormone secretagogue by Dr.Bowers.Iwasdeeplyimpressedtoknowthatmymentor,Dr.HisayukiMatsuo got acquainted with Dr. Bowers, since Matsuo and Bowers worked in Tulane University with Dr. Andrew Schally, a Nobel prize winner for his discovery of hypothalamic peptide hormones. The second breakthrough was the identification ofthegrowthhormonesecretagoguereceptor.TheworkperformedbyDr.Howard fromMerckresearchlaboratorieswasnotforthefaintheartedandrequiredelegant techniques for cloning the receptor. Without the identification of the growth hormone secretagogue receptor, Ghrelin would not have been discovered. v vi Foreword The third breakthrough was the discovery of Ghrelin by my group. The tissue, from which Ghrelin was discovered, was surprisingly in stomach. These results suggestthatstomachisnotonlyadigestiveorganbutalsoanendocrineorganthat secretes growth hormone releasing peptide. The fourth breakthrough was the role of Ghrelin as an orexigenic peptide from peripheral tissue. These results were reported almost at the same time by different independent groups. The fifth breakthroughwastheidentificationofGhrelinO-acyltransferase(GOAT),Ghrelin O-acyltransferase, which is an acyltransferase specific for acyl-modification of Ghrelin. The identification of GOAT was performed by two independent groups: onebyDrs.BrownandGoldstein,theNobelprizewinnersfromTexasUniversity, and another by Dr. Gutierrez from Eli Lilly. All these breakthroughs progressed the research of Ghrelin and contributed to more than 6,000 published papers on Ghrelin. Finally, I hope that this book will provide the readers with an up-to-date knowledge on the role of Ghrelin in the central nervous system and attract many researchers to join the study of Ghrelin. Kurume Masayasu Kojima Preface In 1996, another G-protein coupled receptor (GPCR) was discovered which was added to the ever-increasing list of the seven-transmembrane receptor class: the growth hormone secretagogue receptor. The popularity of this receptor took a U-turn after 1999 when its endogenous ligand Ghrelin was discovered as a result of what is now known as a classical case of reverse pharmacology. The vast pleiotropic physiological properties this ligand presented following its binding to the growth hormone secretagogue receptor led to the latter to be nicknamed ‘the Ghrelin receptor’. This is detailed by Prof. Kojima in his foreword, for which we areextremelyhonoredtohaveasanintroductiontoourbook.TheGhrelinreceptor is located in various central and peripheral organs, and is present in different species, which has allowed numerous scientists from entirely different fields to feverishly understand this receptor system. It has taken years for Ghrelin researchers to start understanding the complicated nature of the Ghrelin receptor, having properties that few other GPCRs encompass. This is not a straightforward receptor system, and this was what compelled us to bring together this book that solely focuses on the Ghrelin receptors present in the central nervous system. The sole aim of this book was to congregate the known different roles of Ghrelin receptors present in the central nervous system, together with a detailed explanation on the intrinsic properties of the receptor itself. The 13 different chapters in this book, each penned by experts in the field, give a complete overview ofwhatis known to date with regards to this receptorin the brain. This concise gathering is aimed as a valuable reference for students, neuroscientists, pharmacologists, and physicians who are working in the Ghrelin receptor field or else are interested in the potential of this receptor axis in the clinical setting. We would like to thank Springer and its publishing editor for this series for giving us the opportunity to develop and publish this book as part of their ‘TheReceptors’series.Lastbutnotleast,wewouldalsoliketoexpressoursincere appreciation to all the chapter authors. This book would not exist were it not for theeffortsofallauthorswhoenthusiasticallycontributedthechaptersofthisbook, for which we are very grateful. Brussels, Ghent, Belgium Jeanelle Portelli Brussels, Belgium Ilse Smolders vii Contents Part I The Ghrelin Receptor Isoforms 1 Constitutive Activity of the Ghrelin Receptor . . . . . . . . . . . . . . . 3 Jacek Mokrosin´ski, Andreas Nygaard Madsen and Birgitte Holst 2 Homodimerization and Heterodimerization of the Ghrelin Receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Alessandro Laviano and Alessia Mari Part II Mechanisms of Ghrelin’s Action 3 The Role of the Ghrelin Receptor in Appetite and Energy Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Romana Stark and Zane B. Andrews 4 The Vagus Nerve and Ghrelin Function . . . . . . . . . . . . . . . . . . . 53 Yukari Date Part III Ghrelin Receptors in Food and Drug Addictive Mechanisms 5 Central Ghrelin Receptors and Food Intake . . . . . . . . . . . . . . . . 65 Mario Perello and Jesica Raingo 6 The Ghrelin Receptor: A Novel Therapeutic Target for Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Harriët Schellekens, Timothy G. Dinan and John F. Cryan 7 Ghrelin Receptor Antagonism as a Potential Therapeutic Target for Alcohol Use Disorders: A Preclinical Perspective . . . . 123 Elisabet Jerlhag and Jörgen A. Engel ix x Contents 8 Clinical Research on the Ghrelin Axis and Alcohol Consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Allison A. Feduccia and Lorenzo Leggio Part IV Ghrelin Plays a Role in Various Physiological and Pathophysiological Brain Functions 9 Ghrelin and Sleep Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Éva Szentirmai and Levente Kapás 10 Ghrelin and Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Nicolas Kunath and Martin Dresler 11 Ghrelin Receptors and Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . 177 Jeanelle Portelli, Ann Massie, Jessica Coppens and Ilse Smolders 12 Ghrelin Plays a Role in Various Physiological and Pathophysiological Brain Functions . . . . . . . . . . . . . . . . . . . 191 Sarah J. Spencer 13 Ghrelin and Parkinson’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . 205 Marcus M. Unger and Wolfgang H. Oertel Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 Contributors ZaneB.Andrews DepartmentofPhysiology,MonashUniversity,Clayton,VIC, Australia Jessica Coppens Department of Pharmaceutical Chemistry, Center for Neuro- sciences, Drug Analysis and Drug Information, Vrije Universiteit Brussel, Brussels, Belgium John F.Cryan Foodfor Health Ireland,UniversityCollege Cork,Cork, Ireland; Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Univer- sity College Cork, Cork, Ireland; Deparment of Anatomy and Neuroscience, Western Gateway Building, University College Cork, Cork, Ireland Yukari Date Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan Timothy G. Dinan Food for Health Ireland, University College Cork, Cork, Ireland; Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Psychiatry, University College Cork, Cork, Ireland Martin Dresler Max Planck Institute of Psychiatry, Munich, Germany Jörgen A. Engel Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Allison A. Feduccia Section on Clinical Psychoneuroendocrinology and Neuro- psychopharmacology, NIAAA and NIDA National Institutes of Health, Bethesda, MD, USA Birgitte Holst Department of Neuroscience and Pharmacology and NNF Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen N, Denmark Elisabet Jerlhag Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden xi
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