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Encyclopedia of Molecular Pharmacology
STEFAN OFFERMANNS AND WALTER ROSENTHAL (Eds.)
Encyclopedia of Molecular Pharmacology(2nd edition)
With 487 Figures* and 171 Tables
*For color figures please see our Electronic Reference on www.springerlink.com
Editors:Professor Dr. Stefan Offermanns Professor Dr. Walter Rosenthal
Pharmakologisches InstitutUniversität HeidelbergIm Neuenheimer Feld 366D-69120 [email protected]Leibniz-Institut für Molekulare Pharmakologie (FMP)Campus Berlin-BuchRobert-Rössle-Str. 10D-13125 [email protected]
A C.I.P. Catalog record for this book is available from the Library of Congress
ISBN: 978-3-540-38916-3This publication is available also as:Electronic publication under ISBN 978-3-540-38918-7 andPrint and electronic bundle under ISBN 978-3-540-38921-7
Library of Congress Control Number: 2008921487
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights oftranslation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks.Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, inits current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under theGerman Copyright Law.
© Springer-Verlag Berlin Heidelberg New York 2008
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names areexempt from the relevant protective laws and regulations and therefore free for general use.
Product liability: The publishers cannot guarantee the accuracy of any information about the application of operative techniques andmedications contained in this book. In every individual case the user must check such information by consulting the relevant literature.
Springer is part of Springer Science+Business Media
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Printed on acid-free paper SPIN: 191230 2109 — 5 4 3 2 1 0
Preface to the First Edition
The era of pharmacology, the science concerned with the understanding of drug action, began only about 150 yearsago when Rudolf Buchheim established the first pharmacological laboratory in Dorpat (now, Tartu, Estonia). Sincethen, pharmacology has always been a lively discipline with “open borders”, reaching out not only to other lifesciences such as physiology, biochemistry, cell biology and clinical medicine, but also to chemistry and physics.In a rather successful initial phase, pharmacologists devoted their time to describing drug actions either at the singleorgan level or on an entire organism. Over the last few decades, however, research has focused on the molecularmechanisms by which drugs exert their effects. Here, cultured cells or even cell-free systems have served as models.As a consequence, our knowledge of the molecular basis of drug actions has increased enormously. The aim ofEncyclopedic Reference of Molecular Pharmacology is to cover this rapidly developing field.
The reductionist approach described above has made it increasingly important to relate the molecular processesunderlying drug actions to the drug effect on the level of an organ or whole organism. Only this integrated view willallow the full understanding and prediction of drug actions, and enable a rational approach to drug development. Onthe molecular or even atomic level, new disciplines such as bioinformatics and structural biology have evolved.They have gained major importance within the field but are particularly relevant for the rational development anddesign of new drugs. Finally, the availability of the complete genome sequence of an increasing number of speciesprovides a basis for systematic, genome-wide pharmacological research aimed at the identification of new drugtargets and individualised drug treatment (pharmacogenomics and pharmacogenetics). All these aspects areconsidered in this encyclopedia.
The main goal of the Encyclopedia is to provide up-to-date information on the molecular mechanisms of drugaction. Leading experts in the field have provided 159 essays, which form the core structure of this publication.
Most of the essays describe groups of drugs and drug targets, with the emphasis not only on already exploited drugtargets, but also on potential drug targets as well. Several essays deal with the more general principles ofpharmacology, such as drug tolerance, drug addiction or drug metabolism. Others portray important cellularprocesses or pathological situations and describe how they can be influenced by drugs. The essays arecomplemented by more than 1600 keywords, for which links are provided. By looking up the keywords or titles ofessays highlighted in each essay, the reader can obtain further information on the subject. The alphabetical order ofentries makes the Encyclopedia very easy to use and helps the reader to search successfully. In addition, the namesof authors are listed alphabetically, together with the title of their essay, to allow a search by author name.
Apart from very few exceptions, the entries in the main text do not contain drug names in their titles. Instead, drugsthat are commonly used all over the world are listed in the Appendix. Also included in the Appendix are fourextensive sections that contain tables listing proteins such as receptors, transporters or ion channels, which are ofparticular interest as drug targets or modulators of drug action.
The Encyclopedia provides valuable information for readers with different expectations and backgrounds (fromscientists, students and lecturers to informed lay-people) and fills the gap between pharmacology textbooks andspecialized reviews.
All the contributing authors as well as the editors have taken great care to provide up-to-date information. However,inconsistencies or errors may remain, for which we assume full responsibility. We welcome comments, suggestionsor corrections and look forward to a stimulating dialog with the readers of the Encyclopedic Reference of MolecularPharmacology whether their comments concern the content of an individual entry or the entire concept.
We are indebted to our colleagues for their excellent contributions. It has been a great experience, both personallyand scientifically, to interact with and learn from the 200 plus contributing authors. We would also like to thankMs. Hana Deuchert andMs. Katharina Schmalfeld for their excellent and invaluable secretarial assistance during allthe stages of this project. Within Springer-Verlag, we are grateful to Dr. Thomas Mager for suggesting the project andto Frank Krabbes for his technical expertise. Finally, we would like to express our gratitude to Dr. Claudia Langefor successfully managing the project and for her encouraging support. It has been a pleasure to work with her.
Heidelberg/Berlin, June 2003STEFAN OFFERMANNS AND WALTER ROSENTHAL
Preface to the Second Edition
The first edition of the Encyclopedic Reference of Molecular Pharmacologywas well received by its readers, thanksto the excellent work done by the authors, of whom most have contributed to the second edition as well. The basicstructure of the Encyclopedia has remained unchanged. It is primarily based on essays, which have been updated,and their number has been increased to 225 to include many new exciting areas. These essays cover important drugsand drug targets, but also general principles of pharmacology as well as cellular processes and pathologicalsituations which are relevant for drug action. In addition, there are about xy key words linked to the essays. TheEncyclopedia is complemented by an Appendix, which has been greatly enlarged, listing more than 700 drugs andmore than 4,000 proteins that act as receptors, membrane transport proteins, transcription factors, enzymes oradhesion molecules.
During the preparation, we greatly enjoyed the interaction with all our colleagues who contributed to this referencework. It has been a pleasure and an enriching experience to deal with so many facets of pharmacology. We are verythankful to the contributing authors for the careful updating of their essays, and, in particular, we would like toexpress our gratitude to the more than xy new authors who have written excellent essays on novel topics. Finally, wewould like to thank Dr. Michaela Bilic and Simone Giesler from Springer for their enthusiasm throughout theproject and their constant support.
Heidelberg/Berlin, November 2007STEFAN OFFERMANNS AND WALTER ROSENTHAL
List of Contributors
AMY N. ABELL
University of North CarolinaChapel Hill, [email protected]
IAN M. ADCOCK
Imperial [email protected]
GEORGE K. AGHAJANIAN
Yale School of MedicineNew Haven, [email protected]
KLAUS AKTORIES
Institut für Experimentelle und Klinische Pharmakologie undToxikologie, Albert-Ludwigs-Universität [email protected]
NEIL ANDERSON
Department of NeuropharmacologyCopenhagenDenmark
ION ANGHELESCU
Department of Psychiatry and PsychotherapyCharité, [email protected]
LUCIO ANNUNZIATO
Division of Pharmacology, Department of NeuroscienceSchool of Medicine, “Federico II” University of [email protected]
MARINA P. ANTOCH
Department of Molecular and Cancer BiologyRoswell Park Cancer [email protected]
FABIO ANTONIOLI
Department of Biological RegulationThe Weizmann Institute of [email protected]
HELLMUT G. AUGUSTIN
Joint Research Division Vascular Biology of the MedicalFaculty MannheimUniversity of Heidelberg, and the German Cancer ResearchCenter (DKFZ)Mannheim and [email protected]
JOHAN AUWERX
Institut de Génétique et Biologie Moléculaire et Cellulaire-Institut Clinique de la [email protected]
CHRISTIAN AYMANNS
Nephrology Division, Department of Internal Medicine IUniversity HospitalUlmGermany
WILLIAM BABBITT
UCSF School of MedicineSan Francisco, [email protected]
EVELYN BACK
Novartis Pharma GmbHNü[email protected]
MICHAEL BADER
Max Delbrück Center for Molecular Medicine (MDC)Campus [email protected]
CLIFFORD J. BAILEY
School of Life and Health SciencesAston [email protected]
JILLIAN G. BAKER
University of [email protected].
ANDREAS BARTHEL
BG-Kliniken BergmannsheilRuhr-UniversityBochumGermanyAndreas.Barthel@post.rwth-aachen.de
x List of Contributors
HOLGER BASTIANS
Institute for Molecular Biology and Tumor Research (IMT)Philipps-University [email protected]
JOSEPH A. BEAVO
Department of PharmacologyUniversity of WashingtonSeattle, [email protected]
HEINZ BECK
Labor für Experimentelle Epileptologie, Klinik fürEpileptologieUniversitätskliniken [email protected]
CORD-MICHAEL BECKER
Institut für BiochemieEmil-Fischer-Zentrum, Universität Erlangen-Nü[email protected]
JÜRGEN BEHRENS
Nikolaus-Fiebiger-Center for Molecular [email protected]
FABRIZIO BENEDETTI
Department of NeuroscienceUniversity of Turin Medical [email protected]
MARTIN R. BERGER
DKFZ, Toxicology and Chemotherapy UnitIm Neuenheimer [email protected]
FELICITY K. R. BERTRAM
Sackler Institute of Pulmonary PharmacologyKing’s College [email protected]
MARTIN BIEL
Munich Center for Integrated Protein Science CiPSM andDepartment of Pharmacy – Center for Drug ResearchLudwig-Maximilians-Universität MünchenMü[email protected]
HANS K. BIESALSKI
Institute of Biological Chemistry and NutritionUniversity of [email protected]
TIFFANY BLAKE
Laboratory of GI Developmental BiologyDepartment of SurgeryMedicine & Lombardi Cancer CenterGeorgetown UniversityWashington, [email protected]
GREGORY LE BLATCH
Department of Biochemistry, Microbiology andBiotechnologyRhodes UniversityGrahamstownSouth [email protected]
CLARK M. BLATTEIS
University of Tennessee Health Science CenterCollege of MedicineMemphis, [email protected]
ANDREE BLAUKAT
TA Oncology, Merck Serono ResearchMerck [email protected]
MICHAEL BÖHM
Klinik für Innere Medizin IIIHomburg/[email protected]
MICHELLE BOONE
Department of PhysiologyRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
ARNDT BORKHARDT
Children’s University Hospital, Department of PaediatricHaematology & Oncology & Clinical ImmunologyUniversität DüsseldorfDü[email protected]
JACK BOTTING
William Harvey Research InstituteSchool of Medicine and DentistrySt. Bartholomew’s and Royal [email protected]
List of Contributors xi
REGINA BOTTING
William Harvey Research InstituteSchool of Medicine and DentistrySt. Bartholomew’s and Royal [email protected]
STEFAN-MARTIN BRAND-HERRMANN
Leibniz-Institut für ArterioskleroseforschungUniversität MünsterMü[email protected]
MICHAEL BRÄU
Abteilung Anaesthesiologie und Operative IntensivmedizinJustus-Liebig-UniversitätGieß[email protected]
MATTHEW D. BREYER
Division of NephrologyMedical Center, Vanderbilt UniversityNashville, [email protected]
RICHARD M. BREYER
Division of NephrologyMedical Center, Vanderbilt UniversityNashville, [email protected]
JÜRGEN BROCKMÖLLER
Zentrum Pharmakologie und ToxikologieGeorg-August-Universität GöttingenGö[email protected]
MATTHEW D. BROWN
Department of Pathology, Brigham and Women’s HospitalHarvard Medical SchoolBoston, MAUSA
EDWARD M. BROWN
Division of Endocrinology, Diabetes and HypertensionBrigham and Women’s HospitalBoston, [email protected]
EREZ M. BUBLIL
Department of Biological RegulationThe Weizmann Institute of [email protected]
FRED BUNZ
The Sidney Kimmel Comprehensive Cancer Center at JohnsHopkins, The Johns Hopkins School of MedicineBaltimore, [email protected]
RÉMY BURCELIN
Institute of Molecular MedicineINSERM, IFR 31Université Paul [email protected]
GEOFFREY BURNSTOCK
Autonomic Neuroscience CentreRoyal Free and University College Medical [email protected]
AMAN U. BUZDAR
Department of Breast Medical OncologyThe University of Texas, M.D. Anderson Cancer CenterHouston, [email protected]
PATRICE D. CANI
Institute of Molecular MedicineINSERM, IFR 31Université Paul SabatierToulouseFrance
PATRICK J. CASEY
Duke University Medical CenterDurham, [email protected]
TAMARA CASTANEDA
Department of PsychiatryObesity Research Center, University of CincinnatiCincinnati, [email protected]
THOMAS K. H. CHANG
Faculty of Pharmaceutical SciencesThe University of British ColumbiaVancouver, [email protected]
DI CHEN
ANZAC Research InstituteThe University of RochesterNY, USA
BENJAMIN N. R. CHEYETTE
University of CaliforniaSan Francisco, [email protected]
xii List of Contributors
RUSSELL COMPTON
School of BiosciencesThe University of [email protected]
MARGARET R. CUNNINGHAM
Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of StrathclydeGlasgow, [email protected]
DAVID CZOCK
Nephrology Division, Department of Internal Medicine IUniversity HospitalUlmGermany
ANTHONY P. DAVENPORT
Clinical Pharmacology UnitUniversity of CambridgeLevel 6, Centre for Clinical Investigation, Addenbrooke’sHospital, Cambridge, CB2 [email protected]
SHAHEEHAH DAWOOD
Department of Breast Medical OncologyThe University of Texas, M.D. Anderson Cancer CenterHouston, [email protected]
WIM DECLERCQ
Department of Molecular BiologyGhent UniversityBelgium
PETER M.T. DEEN
Department of PhysiologyRadboud University Nijmegen Medical CenterNijmegenThe [email protected]
VINCENZO DI MARZO
Endocannabinoid Research Group, Institute of [email protected]
MIREILLE DELHASE
Department of PharmacologyUniversity of CaliforniaSan Diego, [email protected]
STEFAN DHEIN
Universität Leipzig, Herzzentrum LeipzigKlinik für [email protected]
HOLGER J. DOEGE
Eli Lilly & Company, Intergrative BiologyGreenfield, IN [email protected]
ANDREAS DRAGUHN
Institut für Physiologie und PathophysiologieUniversität [email protected]
COLIN ROBERT DUNSTAN
Head, Bone Research ProgramANZAC Research Institute, The University of SydneyConcord, NSWAustralia
ANNE DURKAN
Hospital for Sick ChildrenToronto, ONTCanada
BJARKE EBERT
Department of ElectrophysiologyCopenhagenDenmarkbjeb@lundbeck com
ROBERT EDWARDS
Departments of Neurology and PhysiologyUniversity of California at San FranciscoSan Francisco, [email protected]
MICHEL EICHELBAUM
Dr. Margarete Fischer-Bosch Institute of ClinicalPharmacologyStuttgartGermanymichel.eichelbaum@ikp-stuttgart.de
JOHN H. EXTON
Howard Hughes Medical Institute and Department ofMolecular Physiology and BiophysicsVanderbilt UniversityNashville, [email protected]
SANDRINE FAIVRE
Department of Medical OncologyBeaujon University HospitalClichy CedexFrance
FRANCESCO FALCIANI
School of BiosciencesThe University of [email protected]
List of Contributors xiii
NAPOLEONE FERRARA
Genentech, Inc.South San Francisco, [email protected]
THOMAS J. FEUERSTEIN
Sektion Klinische Neuropharmakologie, NeurozentrumNeurochirurgische Universitä[email protected]
VEIT FLOCKERZI
Institut für Pharmakologie und ToxikologieUniversität des [email protected]
MARYANN FOOTE
M A Foote Associates, Westlake VillageCA and Department of MicrobiologyMonash [email protected]
ULRICH FÖRSTERMANN
Johannes Gutenberg [email protected]
JÜRGEN FRANK
zet - Centre for Alternative and Complementary Methods toAnimal [email protected]
JEAN-MARIE FRERE
Centre d’Ingenierie des ProtéinesUniversity of LiègeLiè[email protected]
CHRISTIAN FREUND
Protein Engineering GroupLeibniz-Institute for Molecular [email protected]
ELKE C. FUCHS
Abteilung Klinische NeurobiologieInterdisziplinäres Zentrum für Neurowissenschaften (IZN)[email protected]
RUTH GEISS-FRIEDLANDER
Department of Biochemie I, Faculty of MedicineUniversity [email protected]
GERD GEISSLINGER
Institut für Klinische Pharmakologie, Klinikum der JohannWolfgang Goethe-Universität Frankfurt am [email protected]
TOM GELDART
Department of Medical OncologySouthampton General [email protected]
NANCY GERITS
Department of Microbiology and VirologyInstitute of Medical Biology, University of [email protected]
PIERRE GERMAIN
Department of Cell Biology and Signal TransductionInstitut de Genetique et de Biologie Moleculaire et Cellulaire(IGBMC)Illkirch [email protected]
STEPHEN J. GETTING
Department of Human and Health Sciences, School ofBiosciencesUniversity of [email protected]
JEAN-MARIE GHUYSEN
Centre d’Ingenierie des ProtéinesUniversity of LiègeLiègeBelgium
ERIC GLASGOW
Laboratory of GI Developmental Biology, Department ofSurgeryMedicine & Lombardi Cancer Center Georgetown UniversityWashington, DCUSA
JENNIFER L. GLICK
Department of PharmacologyUniversity of WashingtonSeattle, [email protected]
MURALI GOPALAKRISHNAN
Global Pharmaceutical Research and DevelopmentAbbott LaboratoriesAbbott Park, [email protected]
xiv List of Contributors
ANDREAS GREINACHER
Ernst-Moritz-Arndt-Universität [email protected]
SERGIO GRINSTEIN
Hospital for Sick ChildrenToronto, [email protected]
HINRICH GRONEMEYER
Department of Cell Biology and Signal TransductionInstitut de Genetique et de Biologie Moleculaire et Cellulaire(IGBMC)Illkirch [email protected]
MARKUS GRUBE
Department of Pharmacology, Center of Pharmacology andExperimental TherapeuticsErnst-Moritz-Arndt University GreifswaldGreifswaldGermany
THOMAS GUDERMANN
Philipps-Universität [email protected]
JULIE M. HALL
Hamner Institutes of Health SciencesResearch Triangle Park, [email protected]
D. GRAHAME HARDIE
College of Life SciencesUniversity of [email protected]
AARON N. HATA
Division of NephrologyMedical Center, Vanderbilt UniversityNashville, TN,USA
JULIA HEAD
Department of Medical OncologySouthampton General [email protected]
LUTZ HEIN
University of [email protected]
UWE HEINEMANN
Johannes-Müller-Institut für PhysiologieUniversitätsklinikum CharitéHumboldt-Universität zu [email protected]
MATTHIAS HEINZE
Protein Engineering GroupLeibniz-Institute for Molecular PharmacologyBerlinGermany
PETER HEISIG
Pharm. Biology and MicrobiologyUniversity of [email protected]
CLAUS W. HEIZMANN
Department of Pediatrics, Division of Clinical Chemistry andBiochemistryUniversity of [email protected]
RICARDO HERMOSILLA
Department of Molecular Pharmacology and Cell BiologyCharité Medical University [email protected]
MÉLANIE HÉROULT
Joint Research Division Vascular Biology of the MedicalFaculty MannheimUniversity of Heidelberg, and the German Cancer ResearchCenter (DKFZ)Mannheim and HeidelbergGermany
PETER HERRLICH
Leibniz Institute for Age Research – [email protected]
HEIKO HERWALD
Lund [email protected]
ISABELLA HEUSER
Department of Psychiatry and PsychotherapyCharité, [email protected]
List of Contributors xv
STEPHEN J. HILL
University of [email protected]
MARIUS C. HOENER
F. Hoffmann-La Roche, Pharmaceuticals Division,Discovery [email protected]
FRANZ HOFMANN
Institut für Pharmakologie und ToxikologieTU MünchenMü[email protected]
VOLKER HÖLLT
Otto-von-Guericke-Universität [email protected]
HELMUT HOLTMANN
Rudolf-Buchheim-Institut für PharmakologieFrankfurter Straße 107D-35392 Gieß[email protected]
LÁSZLÓ HOMOLYA
Research Group of Membrane Biology, Hungarian Academyof SciencesHungary
RICHARD HORUK
Department of ImmunologyBerlex BiosciencesRichmond [email protected]
SANDER M. HOUTEN
Laboratory Genetic Metabolic DiseasesAcademic Medical CenterAmsterdamThe [email protected]
DANIEL HOYER
Psychiatry/Neuroscience ResearchNovartis Institutes for Biomedical Research [email protected]
NORBERT HÜBNER
MDC for Molecular [email protected]
CHRISTINE HUPPERTZ
Pharma ResearchNovartis Pharma [email protected]
ANDREA HUWILER
pharmazentrum frankfurtJohann Wolfgang Goethe-Universität Frankfurt am [email protected]
KEIJI IMOTO
National Institute for Physiological Sciences and School ofLife ScienceThe Graduate University for Advanced [email protected]
KIYOMI ITODepartment of Clinical PharmacokineticsHoshi UniversityTokyo, [email protected]
KENNETH A. JACOBSON
Molecular Recognition Section, Laboratory of BioorganicChemistry, National Institute of Diabetes Digestive andKidney DiseasesNational Institutes of HealthBethesda, [email protected]
REINHARD JAHN
Max-Planck-Institut für biophysikalische ChemieGö[email protected]
ELISABETH M. JEANCLOS
Universitätsklinikum DüsseldorfDü[email protected]
THOMAS J. JENTSCH
Leibniz-Institut für Molekulare Pharmakologie (FMP) andMax-Delbrück-Centrum für Molekulare Medizin (MDC)[email protected]
GARY L. JOHNSON
University of North CarolinaChapel Hill, [email protected]
ROGER A. JOHNSON
Department of Physiology and BiophysicsState University of New YorkNew York, [email protected]
xvi List of Contributors
HANS-GEORG JOOST
Department of PharmacologyGerman Institute of Human [email protected]
THOMAS JUNGHANSS
Section of Clinical Tropical MedicineUniversity Hospital HeidelbergHeidelbergGermanyThomas.Junghanss@urz.uni-heidelberg.de
VOLKHARD KAEVER
Institute of Pharmacology, Medical School [email protected]
SHITIJ KAPUR
PET Centre - Schizophrenia DivisionCentre for Addiction and Mental HealthToronto, [email protected]
JOHN J. P. KASTELEIN
Department of Vascular MedicineAcademic Medical Center, University of AmsterdamAmsterdamThe [email protected]
STEPHAN KELLENBERGER
Département de pharmacologie et de toxicologie del’Université[email protected]
FRIEDER KELLER
Nephrology Division, Department of Internal Medicine IUniversity [email protected]
TERRY P. KENAKIN
Receptor BiochemistryGlaxo Wellcome ResearchResearch Triangle Park, [email protected]
ELAINE F. KENNY
School of Biochemistry and ImmunologyTrinity College [email protected]
KRISTOF KERSSE
Department of Molecular BiologyGhent UniversityBelgium
HEIKO KILTER
Klinik für Innere Medizin IIIHomburg/[email protected]
PATRICK KITABGI
INSERM U732/Université Pierre et Marie CurieHopital St-AntoineParis cedex [email protected]
SUSANNE KLUMPP
Institut für Pharmazeutische und Medizinische ChemieWestfälische Wilhelms-UniversitätMü[email protected]
ENNO KLUSSMANN
Leibniz-Institut fürMolekulare Pharmakologie Department ofMolecular Pharmacology and Cell BiologyCharitè-Universitätsmedizin [email protected]
CLAUDE KNAUF
Institute of Molecular MedicineINSERM, IFR 31Université Paul SabatierToulouseFrance
KLAUS-PETER KNOBELOCH
Leibniz-Institut für Molekulare [email protected]
BRIAN K. KOBILKA
Stanford University Medical SchoolStanford, [email protected]
DORIS KOESLING
Pharmakologie und ToxikologieRuhr-Universität [email protected]
SPIRO M. KONSTANTINOV
Department of Pharmacology and ToxicologyMedical University in Sofia, Faculty of [email protected]
KENNETH S. KORACH
National Institute of Environmental Health SciencesResearch Triangle Park, [email protected]
List of Contributors xvii
MICHAEL KRACHT
Medizinische Hochschule [email protected]
EBERHARD KRAUSE
Leibniz-Institut für Molekulare [email protected]
GERD KRAUSE
Forschungsinstitut für Molekulare PharmakologieCampus [email protected]
HANS-GEORG KRÄUSSLICH
Abteilung VirologieUniversitätsklinikum HeidelbergHeidelbergGermanyHans-Georg_Kraeusslich@med.uni-heidelberg.de
REINHOLD KREUTZ
Freie Universität [email protected]
KERSTIN KRIEGLSTEIN
Universität GöttingenGö[email protected]
JOSEF KRIEGLSTEIN
Westfälische Wilhelms-Universität, Institut fürPharmazeutische und Medizinische ChemieMü[email protected]
ANJA KRIPPNER-HEIDENREICH
Institut of Cellular MedicineNewcastle UniversityNewcastle upon [email protected]
HEYO K. KROEMER
Department of Pharmacology, Center of Pharmacology andExperimental TherapeuticsErnst-Moritz-Arndt University [email protected]
ROHINI KUNER
Institute for PharmacologyUniversity of [email protected]
NAGOMI KUREBAYASHI
Department of PharmacologyJuntendo University School of [email protected]
THORSTEN LANG
Max-Planck-Institut für biophysikalische ChemieGö[email protected]
MICHAEL LANZER
Department of ParasitologyUniversity Hospital [email protected]
DAVID S. LATCHMAN
Institute of Child HealthUniversity College [email protected]
MOGENS LYTKEN LARSEN
Odense University Hospital and Department of CardiologyAalborg [email protected]
ALESSANDRO LECCI
Clinical Research Dept (AL) and Direction (CAM) ofMenarini [email protected]
ALAN R. LEFF
Department of MedicineUniversity of ChicagoChicago, [email protected]
PETER LIBBY
Division of Cardiovascular Medicine, Department ofMedicineBrigham and Women’s Hospital, Harvard Medical SchoolBoston, [email protected]
LOTHAR LINDEMANN
F. Hoffmann-La Roche, Pharmaceuticals Division, [email protected]
JENS P. LINGE
Joint Research Centre of the European CommissionIspraItaly
xviii List of Contributors
MARIA LIOUMI
School of BiosciencesThe University of [email protected]
ROBBIE LOEWITH
Département de Biologie MoléculaireUniversité de Genè[email protected]
MARTIN J. LOHSE
Universität WürzburgWü[email protected]
KATHERINE S. LONG
Department of Molecular BiologyUniversity of [email protected]
ANATOLI N. LOPATIN
University of MichiganAnn Arbor, [email protected]
JOURN LÖTSCH
Institut für Klinische Pharmakologie, Klinikum der JohannWolfgang Goethe-Universität Frankfurt am [email protected]
MARIE-GABRIELLE LUDWIG
Novartis Institutes for Biomedical [email protected]
RAYMUND MACHOVICH
Department of Medical BiochemistrySemmelweis [email protected]
FERNANDO MACIAN
Albert Einstein College of MedicineBronx, [email protected]
CARLO ALBERTO MAGGI
Clinical Research Dept (AL) and Direction (CAM) ofMenarini [email protected]
JANET J. MAGUIRE
Clinical Pharmacology UnitUniversity of CambridgeLevel 6, Centre for Clinical Investigation, Addenbrooke’sHospitalCambridgeUK
DAVID C. MAMO
PET Centre - Schizophrenia DivisionCentre for Addiction and Mental HealthToronto, [email protected]
PEKKA T. MÄNNISTÖ
Division of Pharmacology and Toxicology, Faculty ofPharmacyUniversity of [email protected]
CHRISTIAN MARTIN
Institute of Experimental and Clinical Pharmacology andToxicologyUniversitätsklinikum [email protected]
MICHAEL U. MARTIN
Immuology FB 08Justus-Liebig-University [email protected]
FRAUKE MELCHIOR
Department of Biochemie I, Faculty of MedicineUniversity [email protected]
PIERANTONIO MENNA
Department of Drug Sciences and Center of Excellence onAgingG. d’Annunzio University School of MedicineChietiItaly
AXEL H. MEYER
Abteilung Klinische NeurobiologieInterdisziplinäres Zentrum für Neurowissenschaften (IZN)[email protected]
DIETER K. MEYER
Institut für Experimentelle und Klinische Pharmakologie undToxikologieAlbert-Ludwigs-Universität [email protected]
List of Contributors xix
THOMAS MEYER
Abteilung Psychosomatische Medizin und PsychotherapieUniversität [email protected]
DAGMAR MEYER ZU HERINGDORF
Institut für PharmakologieUniversität [email protected]
WOLFGANG MEYERHOF
Department of Molecular GeneticsGerman Institute of Human Nutrition [email protected]
MARTIN C. MICHEL
Academisch Medisch CentrumAmsterdamThe [email protected]
NICO MICHEL
Universitätsklinikum Heidelberg, [email protected]
GIORGIO MINOTTI
Department of Drug Sciences and Center of Excellence onAgingG. d’Annunzio University School of [email protected]
BIBHUTI MISHRA
Laboratory of GI Developmental Biology, Department ofSurgeryMedicine & Lombardi Cancer Center Georgetown UniversityWashington, DCUSA
LOPA MISHRA
Veterans Affairs Medical CenterWashington, [email protected]
FREDERICK JOHN MITCHELSON
Department of PharmacologyUniversity of MelbourneMelbourne, [email protected]
UGO MOENS
University of Tromso, Department of Microbiology andVirologyInstitute of Medical Biology, University of [email protected]
HANNAH MONYER
Abteilung Klinische NeurobiologieInterdisziplinäres Zentrum für Neurowissenschaften (IZN)[email protected]
GREG B. G. MOORHEAD
Department of Biological SciencesUniversity of CalgaryCalgary, [email protected]
GEORGE MORSTYN
M A Foote Associates, Westlake Village, CA and Departmentof MicrobiologyMonash [email protected]
SHAKER A. MOUSA
Albany College of PharmacyAlbany, [email protected]
K. S. MÜHLBERG
III. Medical DepartmentUniversity of [email protected]
BARBARA MÜLLER
Abteilung VirologieUniversitätsklinikum [email protected]
JUDITH M. MÜLLER
Universitäts-Frauenklinik und Zentrum für KlinischeForschung, Klinikum der Universität [email protected]
MARTIN MÜLLER
Deutsches Krebsforschungszentrum [email protected]
ROLF MÜLLER
Institute for Molecular Biology and Tumor Research (IMT)Philipps-University [email protected]
WERNER MÜLLER-ESTERL
University of Frankfurt Medical [email protected]
xx List of Contributors
GERD MULTHAUP
Institut für Chemie und BiochemieFreie Universität [email protected]
NILDA M. MUÑOZ
Department of MedicineUniversity of ChicagoChicago, [email protected]
LISA MUNTER
Institut für Chemie und BiochemieFreie Universität [email protected]
TAKASHI MURAYAMA
Department of PharmacologyJuntendo University School of [email protected]
CHRISTIAN NANOFF
Institut für Pharmakologie, and Christian Pifl, Zentrum fürHirnforschungMedizinische Universität [email protected]
PAUL A. NEGULESCU
Vertex Pharmaceuticals IncorporatedSan Diego, [email protected]
JENS NEUMEYER
Institut für Zellbiologie und ImmunologieUniversität [email protected]
ALEXANDRA C. NEWTON
Department of PharmacologyUniversity of California at San DiegoLa Jolla, [email protected]
COLIN G. NICHOLS
Washington University School of MedicineSt. Louis, [email protected]
MICHAEL NILGES
Unité de Bio–Informatique StructuraleInstitut [email protected]
DONATUS NOHR
Institute of Biological Chemistry and NutritionUniversity of [email protected]
HANS-PETER NOTHACKER
Department of PharmacologyUniversity of CaliforniaIrvine, [email protected]
ASTRID NOVOSEL
Children’s University Hospital, Department of PaediatricHaematology & Oncology & Clinical ImmunologyUniversität DüsseldorfDü[email protected]
BERND NÜRNBERG
Universitätsklinikum DüsseldorfDü[email protected]
JAMES N. OAK
Centre for Addiction & Mental HealthUniversity of TorontoToronto, [email protected]
STEFAN OFFERMANNS
Institute of PharmacologyUniversity of HeidelbergHeidelbergGermanystefan.offermanns@pharma.uni-heidelberg.de
YASUO OGAWA
Department of PharmacologyJuntendo University School of [email protected]
NATHAN D. OKERLUND
University of CaliforniaSan Francisco, CAUSA
ALEXANDER OKSCHE
Mundipharma Research [email protected]
GISELA OLIAS
Department of Molecular GeneticsGerman Institute of Human [email protected]
List of Contributors xxi
LUKE A. J. O’NEILL
School of Biochemistry and ImmunologyTrinity College [email protected]
HARTMUT OSCHKINAT
Leibniz-Institut für Molekulare [email protected]
RENÉ R. S. PACKARD
Division of Cardiovascular Medicine, Department ofMedicineBrigham and Women’s Hospital, Harvard Medical SchoolBoston, [email protected]
MATHIVANAN PACKIARAJAN
Lundbeck Research USAParamus, [email protected]
CLIVE P. PAGE
Sackler Institute of Pulmonary PharmacologyKing’s College [email protected]
RALPH PASCHKE
III. Medical DepartmentUniversity of [email protected]
JÖRG PETERS
Physiologisches Institut der Universität [email protected]
ALEXANDER PFEIFER
University of BonnInstitute of Pharmacology and [email protected]
JOSEF PFEILSCHIFTER
Pharmazentrum FrankfurtJohann Wolfgang Goethe-Universität Frankfurt am [email protected]
JEAN-PHILIPPE PIN
Institut de Génomique FonctionnelleCNRS UMR5203, INSERM U661Universités de Montpellier 1&[email protected]
JANE A. PINAIRE
Lilly Research LaboratoriesEli Lilly and CompanyIndiana, [email protected]
SARAH L. PITKIN
Clinical Pharmacology UnitUniversity of CambridgeLevel 6, Centre for Clinical Investigation, Addenbrooke’sHospitalCambridgeUK
ROBIN PLEVIN
Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of [email protected]
EREZ PODOLY
The Life Sciences InstituteThe Hebrew University of JerusalemIsrael
ANNEMARIE POLAK
F. Hoffmann-La Roche LtdAesch, [email protected]
YVES POMMIER
Laboratory of Molecular Pharmacology, Center for CancerResearchNational Cancer Institute, National Institutes of HealthBethesda, [email protected]
OLAF PONGS
Institut für Neurale Signalverarbeitung, Zentrum fürMolekulare Neurobiologie [email protected]
BERND PÖTZSCH
Universitätsklinikum BonnBonnGermany
IRENE PUGA
Albert Einstein College of MedicineBronx, NYUSA
JÖRG RADEMANN
Leibniz Institut für Molekulare Pharmakologie (FMP)[email protected]
xxii List of Contributors
DANIEL J. RADER
Institute for Translational Medicine and TherapeuticsUniversity of Pennsylvania School of MedicinePhiladelphia, [email protected]
NEIL D. RAWLINGS
Wellcome Trust Sanger Institute, Wellcome Trust GenomeCampusHinxton, [email protected]
ERIC RAYMOND
Department of Medical OncologyBeaujon University HospitalClichy [email protected]
HOLGER M. REICHARDT
Department of Cellular and Molecular ImmunologyUniversity of GöttingenGö[email protected]
ANNE REIFEL-MILLER
Lilly Research LaboratoriesEli Lilly and CompanyIndianapolis, [email protected]
RICHARD REIMER
Department of Neurology and Neurological SciencesStanford UniversityStanford, [email protected]
CONSTANZE REINHARD
K.U.Leuven and [email protected]
YVONNE REISS
Joint Research Division Vascular Biology of the MedicalFaculty MannheimUniversity of Heidelberg, and the German Cancer ResearchCenter (DKFZ)Mannheim and HeidelbergGermany
THOMAS RENNÉ
University of WürzburgWü[email protected]
KLAUS RESCH
Institute of PharmacologyHannover Medical [email protected]
ELKE ROEB
GastroenterologyJustus-Liebig-UniversityGieß[email protected]
HANS ROMMELSPACHER
Department of Clinical NeurobiologyUniversity Hospital Benjamin FranklinFree University [email protected]
THOMAS C. ROOS
Reha Klinik Neuharlingersiel, Interdisciplinary Center forDermatology, Pneumology and AllergologyNeuharlingersielGermanyroos@rehaklinik-neuharlingersiel-klinik.de
WALTER ROSENTHAL
Institut für PharmakologieFreie Universität [email protected]
ANA M. ROSSI
Department of PharmacologyUniversity of [email protected]
BERNARD C. ROSSIER
Département de Pharmacologie et de Toxicologie del’Université[email protected]
UWE RUDOLPH
Institute of Pharmacology and ToxicologyUniversity of ZürichZü[email protected]
GEORGE SACHS
David Geffen School of MedicineUniversity of California at Los Angeles and VeteransAdministration Greater Los Angeles Healthcare SystemLos Angeles, [email protected]
List of Contributors xxiii
DAVID B. SACKS
Department of Pathology, Brigham and Women’s HospitalHarvard Medical SchoolBoston, [email protected]
ANAN H. SAID
Laboratory of GI Developmental Biology, Department ofSurgeryMedicine & Lombardi Cancer Center Georgetown UniversityWashington, DCUSA
EMANUELA SALVATORELLI
Department of Drug Sciences and Center of Excellence onAgingG. d’Annunzio University School of MedicineChietiItaly
BALÁZS SARKADI
Research Group of Membrane BiologyHungarian Academy of SciencesHungary
MICHAEL SCHAEFER
Charité – Universitätsmedizin BerlinPharmakologisches InstitutCampus Benjamin [email protected]
GEORGIOS SCHEINER-BOBIS
Institute of Biochemistry and EndocrinologyJustus Liebig University GiessenGiessenGermany
LAURENT SCHILD
Département de Pharmacologie et de Toxicologie del’Université[email protected]
GUDULA SCHMIDT
Institut für Experimentelle und Klinische Pharmakologie undToxikologie, Albert-Ludwigs-Universität [email protected]
ERIK BERG SCHMIDT
Odense University Hospital and Department of CardiologyAalborg [email protected]
GERD SCHMITZ
Institute of Clinical Chemistry and Laboratory MedicineUniversity of [email protected]
JURGEN SCHNERMANN
National Institutes of HealthBethesda, [email protected]
TORSTEN SCHÖNEBERG
Institut für Biochemie, Medizinische FakultätUniversität [email protected]
WILHELM SCHONER
Institute of Biochemistry and EndocrinologyJustus Liebig University GiessenGiessenGermany
ROLAND SCHÜLE
Universitäts-Frauenklinik und Zentrum für KlinischeForschung, Klinikum der Universität [email protected]
RALF SCHÜLEIN
Leibniz-Institut für Molekulare Pharmakologie [email protected]
GÜNTER SCHULTZ
Charité – Universitätsmedizin BerlinPharmakologisches InstitutCampus Benjamin [email protected]
ANNETTE SCHÜRMANN
Department of PharmacologyGerman Institute of Human [email protected]
CHRISTINA SCHWANSTECHER
Molekulare Pharmakologie und ToxikologieTechnische Universität BraunschweigBraunschweigGermanym.schwanstecher@tu-braunschweig.de
MATHIAS SCHWANSTECHER
Molekulare Pharmakologie und ToxikologieTechnische Universität BraunschweigBraunschweigGermanyM.Schwanstecher@tu-braunschweig.de
DIRK SCHWARZER
Leibniz-Institut für Molekulare Pharmakologie (FMP)[email protected]
xxiv List of Contributors
MARKUS JOACHIM SEIBEL
Bone Research ProgramANZAC Research Institute, The University of SydneyConcord, [email protected]
ROLAND SEIFERT
Department of Pharmacology and ToxicologyUniversity of Regensburg, [email protected]
OLIVER SELBACH
Institute of NeurophysiologyHeinrich-Heine University, Dü[email protected]
KLAUS SEUWEN
Novartis Institutes for Biomedical [email protected]
CHAR-CHANG SHIEH
Global Pharmaceutical Research and Development, AbbottLaboratoriesAbbott Park, [email protected]
JAI MOO SHIN
David Geffen School of MedicineUniversity of California at Los Angeles and VeteransAdministration Greater Los Angeles Healthcare SystemLos Angeles, [email protected]
KELLI E. SMITH
Lundbeck Research USAParamus, [email protected]
HERMONA SOREQ
The Life Sciences InstituteThe Hebrew University of [email protected]
NOEMI SOTO-NIEVES
Albert Einstein college of MedicineBronx, NYUSA
RAINER SPANAGEL
Central Institute of Mental [email protected]
ULRICH SPECK
Universitätsklinikum CharitéHumboldt-Universität [email protected]
ANDREAS STAHL
University of CaliforniaDepartment of Nutritional Science and ToxicologyBerkeley, CA 94720, [email protected]
RALF STAHLMANN
Institut für Klinische Pharmakologie und ToxikologieCharité – Universitätsmedizin BerlinCampus Benjamin [email protected]
KLAUS STARKE
Institut für Experimentelle und Klinische Pharmakologie undToxikologieUniversität [email protected]
ALESSANDRA STARLING
Human Genome Research Center, Biosciences InstituteUniversity of São PauloSão PauloBrazil
WIM A. VAN DER STEEG
Department of Vascular MedicineAcademic Medical Center, University of AmsterdamAmsterdamThe [email protected]
CHRISTOPH STEIN
Klinik für Anaesthesiologie und Operative IntensivmedizinFreie Universität BerlinCharité CampusBenjamin [email protected]
CHRISTIAN STEINKÜHLER
IRBM – Merck Research [email protected]
JÖRG STRIESSNIG
Institut für Pharmazie, Abteilung Pharmakologie undToxikologieLeopold-Franzens-Universität [email protected].
List of Contributors xxv
YUICHI SUGIYAMA
Department of Molecular Pharmacokinetics, Graduate Schoolof Pharmaceutical Sciences, The University of TokyoTokyo, [email protected]
GERGELY SZAKÁCS
Institute of EnzymologyHungarian Academy of Sciences
MARTA SZAMEL
Institute of Pharmacology, Medical School [email protected]
GRAZIA TAMMA
Department of General and Environmental PhysiologyUniversity of BariItaly
COLIN W. TAYLOR
Department of PharmacologyUniversity of [email protected]
PETER C. TAYLOR
The Kennedy Institute of Rheumatology Division, Faculty ofMedicineImperial College LondonLondon, [email protected]
ALVIN V. TERRY JRDepartments of Pharmacology and ToxicologyMedical College of GeorgiaAugusta, [email protected]
MARIE-CHRISTIN THISSEN
Westfälische Wilhelms-Universität, Institut fürPharmazeutische und Medizinische ChemieMünsterGermany
NOBORU TODA
Toyama Institute for Cardiovascular Pharmacology [email protected]
ARIE VAN TOL
Department of Cell Biology & GeneticsErasmus University Medical CenterRotterdamThe [email protected]
CHRISTOPHE LE TOURNEAU
Department of Medical OncologyBeaujon University HospitalClichy CedexFrance
PAUL TRAYHURN
Obesity Biology Unit, Division of Metabolic and CellularMedicineUniversity of [email protected]
JAN TUCKERMANN
Leibniz Institute for Age Research – [email protected]
STEFAN UHLIG
Institute of Experimental and Clinical Pharmacology andToxicologyUniversitäsklinikum AachenRWTH [email protected]
HUBERT H. M. VAN TOL
Centre for Addiction & Mental HealthUniversity of TorontoToronto, [email protected]
PETER VANDENABEELE
Department for Molecular Biomedical [email protected]
UWE VINKEMEIER
Chair of Cell BiologyUniversity of Nottingham Medical SchoolSchool of Biomedical SciencesNottingham, NG7 [email protected]
ANDRÁS VÁRADI
Institute of EnzymologyHungarian Academy of [email protected]
GIRISH VYAS
Department of Laboratory MedicineUniversity of CaliforniaSan Francisco, [email protected]
KEITH WAFFORD
Lilly and Co. Eri Wood Manor WindlesshanSurreyUK
KEITH WAFFORD
Merck, Sharp & Dohme Research LaboratoriesHarlow, [email protected]
xxvi List of Contributors
HENNING WALCZAK
Department of Immunology, Division of MedicineImperial College [email protected]
MARY W. WALKER
Lundbeck Research USAParamus, [email protected]
RUI WANG
Lakehead UniversityThunder Bay, [email protected]
THEODORE E. WARKENTIN
Hamilton Regional Laboratory Medicine ProgramHamilton Health Sciences, and Department of Pathologyand Molecular MedicineMichael G. DeGroote School of MedicalMcMaster UniversityHamilton, [email protected]
TANYA M. WATTERS
School of Biochemistry and ImmunologyTrinity College DublinIreland
DAVID J. WAXMAN
Division of Cell and Molecular BiologyDepartment of BiologyBoston UniversityBoston, [email protected]
JÜRGEN WESS
Laboratory of Bioorganic Chemistry, National Institutes ofHealth (NIDDK)Bethesda, [email protected]
BERND WIEDEMANN
Rheinische Friedrich-Wilhelms-Universitä[email protected]
IRITH WIEGAND
Rheinische Friedrich-Wilhelms-Universitä[email protected]
FELIX T. WIELAND
Biochemie-Zentrum HeidelbergUniversity [email protected]
THOMAS E. WILLNOW
Max-Delbrueck-Center for Molecular [email protected]
SUSAN WONNACOTT
Department of Biology and BiochemistryUniversity of [email protected]
THOMAS WORZFELD
Institute of PharmacologyUniversity of HeidelbergHeidelbergGermany
YOSEF YARDEN
Department of Biological RegulationThe Weizmann Institute of [email protected]
MOUSSA B. H. YOUDIM
Technion-Rappaport Faculty of MedicineEva Topf Center of Excellence for NeurodegenerativeDiseasesDepartment of [email protected]
ULRICH M. ZANGER
Dr. Margarete Fischer-Bosch Institute of [email protected]
MAYANA ZATZ
Human Genome Research Center, Biosciences InstituteUniversity of São PauloSão [email protected]
RAINER ZAWATZKY
Deutsches Krebsforschungszentrum [email protected]
HONG ZHOU
Bone Research ProgramANZAC Research Institute, The University of SydneyConcord, NSWAustralia
List of Contributors xxvii
HEIKE ZIMDAHL
Boehringer IngelheimPharma GmbH & Co [email protected]
RICHARD ZIMMERMANN
Medizinische Biochemie und MolekularbiologieUniversität des [email protected]
