molecular pharmacology(MAZEN SAEED) PDF

Preview

Summary

Encyclopedia of Molecular Pharmacology S TEFAN O FFERMANNS AND WALTER R OSENTHAL (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 Profe...

Description

Encyclopedia of Molecular Pharmacology

S TEFAN O FFERMANNS

AND

WALTER R OSENTHAL (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 Pharmakologisches Institut Universität Heidelberg Im Neuenheimer Feld 366 D-69120 Heidelberg Germany [email protected]

Professor Dr. Walter Rosenthal Leibniz-Institut für Molekulare Pharmakologie (FMP) Campus Berlin-Buch Robert-Rössle-Str. 10 D-13125 Berlin Germany [email protected]

A C.I.P. Catalog record for this book is available from the Library of Congress ISBN: 978-3-540-38916-3 This publication is available also as: Electronic publication under ISBN 978-3-540-38918-7 and Print 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 of translation, 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, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German 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 are exempt 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 and medications 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 springer.com 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 years ago when Rudolf Buchheim established the first pharmacological laboratory in Dorpat (now, Tartu, Estonia). Since then, pharmacology has always been a lively discipline with “open borders”, reaching out not only to other life sciences 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 single organ level or on an entire organism. Over the last few decades, however, research has focused on the molecular mechanisms 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 of Encyclopedic 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 processes underlying drug actions to the drug effect on the level of an organ or whole organism. Only this integrated view will allow the full understanding and prediction of drug actions, and enable a rational approach to drug development. On the 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 and design of new drugs. Finally, the availability of the complete genome sequence of an increasing number of species provides a basis for systematic, genome-wide pharmacological research aimed at the identification of new drug targets and individualised drug treatment (pharmacogenomics and pharmacogenetics). All these aspects are considered in this encyclopedia. The main goal of the Encyclopedia is to provide up-to-date information on the molecular mechanisms of drug action. 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 drug targets, but also on potential drug targets as well. Several essays deal with the more general principles of pharmacology, such as drug tolerance, drug addiction or drug metabolism. Others portray important cellular processes or pathological situations and describe how they can be influenced by drugs. The essays are complemented by more than 1600 keywords, for which links are provided. By looking up the keywords or titles of essays highlighted in each essay, the reader can obtain further information on the subject. The alphabetical order of entries makes the Encyclopedia very easy to use and helps the reader to search successfully. In addition, the names of 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, drugs that are commonly used all over the world are listed in the Appendix. Also included in the Appendix are four extensive sections that contain tables listing proteins such as receptors, transporters or ion channels, which are of particular interest as drug targets or modulators of drug action. The Encyclopedia provides valuable information for readers with different expectations and backgrounds (from scientists, students and lecturers to informed lay-people) and fills the gap between pharmacology textbooks and specialized 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, suggestions or corrections and look forward to a stimulating dialog with the readers of the Encyclopedic Reference of Molecular Pharmacology 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 personally and scientifically, to interact with and learn from the 200 plus contributing authors. We would also like to thank Ms. Hana Deuchert and Ms. Katharina Schmalfeld for their excellent and invaluable secretarial assistance during all the stages of this project. Within Springer-Verlag, we are grateful to Dr. Thomas Mager for suggesting the project and to Frank Krabbes for his technical expertise. Finally, we would like to express our gratitude to Dr. Claudia Lange for successfully managing the project and for her encouraging support. It has been a pleasure to work with her. Heidelberg/Berlin, June 2003 STEFAN OFFERMANNS AND WALTER ROSENTHAL

Preface to the Second Edition The first edition of the Encyclopedic Reference of Molecular Pharmacology was well received by its readers, thanks to the excellent work done by the authors, of whom most have contributed to the second edition as well. The basic structure 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 drugs and drug targets, but also general principles of pharmacology as well as cellular processes and pathological situations which are relevant for drug action. In addition, there are about xy key words linked to the essays. The Encyclopedia is complemented by an Appendix, which has been greatly enlarged, listing more than 700 drugs and more than 4,000 proteins that act as receptors, membrane transport proteins, transcription factors, enzymes or adhesion molecules. During the preparation, we greatly enjoyed the interaction with all our colleagues who contributed to this reference work. It has been a pleasure and an enriching experience to deal with so many facets of pharmacology. We are very thankful to the contributing authors for the careful updating of their essays, and, in particular, we would like to express our gratitude to the more than xy new authors who have written excellent essays on novel topics. Finally, we would like to thank Dr. Michaela Bilic and Simone Giesler from Springer for their enthusiasm throughout the project and their constant support. Heidelberg/Berlin, November 2007 STEFAN OFFERMANNS AND WALTER ROSENTHAL

List of Contributors A MY N. A BELL University of North Carolina Chapel Hill, NC USA [email protected] I AN M. A DCOCK Imperial College London UK [email protected] G EORGE K. A GHAJANIAN Yale School of Medicine New Haven, CT USA [email protected] K LAUS A KTORIES Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg Freiburg Germany [email protected] N EIL A NDERSON Department of Neuropharmacology Copenhagen Denmark I ON A NGHELESCU Department of Psychiatry and Psychotherapy Charité, CBF Berlin Germany [email protected] L UCIO A NNUNZIATO Division of Pharmacology, Department of Neuroscience School of Medicine, “Federico II” University of Naples Naples Italy [email protected] M ARINA P. A NTOCH Department of Molecular and Cancer Biology Roswell Park Cancer Institute NY USA [email protected] FABIO A NTONIOLI Department of Biological Regulation The Weizmann Institute of Science Rehovot Israel [email protected]

H ELLMUT G. A UGUSTIN Joint Research Division Vascular Biology of the Medical Faculty Mannheim University of Heidelberg, and the German Cancer Research Center (DKFZ) Mannheim and Heidelberg Germany [email protected] J OHAN A UWERX Institut de Génétique et Biologie Moléculaire et CellulaireInstitut Clinique de la Souris Illkirch France [email protected] C HRISTIAN AYMANNS Nephrology Division, Department of Internal Medicine I University Hospital Ulm Germany W ILLIAM B ABBITT UCSF School of Medicine San Francisco, CA USA [email protected] E VELYN B ACK Novartis Pharma GmbH Nürnberg Germany [email protected] M ICHAEL B ADER Max Delbrück Center for Molecular Medicine (MDC) Campus Berlin-Buch Germany [email protected] C LIFFORD J. B AILEY School of Life and Health Sciences Aston University Birmingham UK [email protected] J ILLIAN G. B AKER University of Nottingham UK [email protected]. A NDREAS B ARTHEL BG-Kliniken Bergmannsheil Ruhr-University Bochum Germany [email protected]

x

List of Contributors

H OLGER B ASTIANS Institute for Molecular Biology and Tumor Research (IMT) Philipps-University Marburg Germany [email protected] J OSEPH A. B EAVO Department of Pharmacology University of Washington Seattle, WA USA [email protected] H EINZ B ECK Labor für Experimentelle Epileptologie, Klinik für Epileptologie Universitätskliniken Bonn Bonn Germany [email protected] C ORD -M ICHAEL B ECKER Institut für Biochemie Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg Erlangen Germany [email protected] J ÜRGEN B EHRENS Nikolaus-Fiebiger-Center for Molecular Medicine Erlangen Germany [email protected] FABRIZIO B ENEDETTI Department of Neuroscience University of Turin Medical School Turin Italy [email protected]

H ANS K. B IESALSKI Institute of Biological Chemistry and Nutrition University of Hohenheim Stuttgart Germany [email protected] T IFFANY B LAKE Laboratory of GI Developmental Biology Department of Surgery Medicine & Lombardi Cancer Center Georgetown University Washington, DC USA [email protected] G REGORY L E B LATCH Department of Biochemistry, Microbiology and Biotechnology Rhodes University Grahamstown South Africa [email protected] C LARK M. B LATTEIS University of Tennessee Health Science Center College of Medicine Memphis, TN USA [email protected] A NDREE B LAUKAT TA Oncology, Merck Serono Research Merck KGaA Darmstadt Germany [email protected] M ICHAEL B ÖHM Klinik für Innere Medizin III Homburg/Saar Germany [email protected]

M ARTIN R. B ERGER DKFZ, Toxicology and Chemotherapy Unit Im Neuenheimer Feld Heidelberg Germany [email protected]

M ICHELLE B OONE Department of Physiology Radboud University Nijmegen Medical Center Nijmegen The Netherlands

F ELICITY K. R. B ERTRAM Sackler Institute of Pulmonary Pharmacology King’s College London London UK [email protected]

A RNDT B ORKHARDT Children’s University Hospital, Department of Paediatric Haematology & Oncology & Clinical Immunology Universität Düsseldorf Düsseldorf Germany [email protected]

M ARTIN B IEL Munich Center for Integrated Protein Science CiPSM and Department of Pharmacy – Center for Drug Research Ludwig-Maximilians-Universität München München Germany [email protected]

J ACK B OTTING William Harvey Research Institute School of Medicine and Dentistry St. Bartholomew’s and Royal London London UK [email protected]

List of Contributors

R EGINA B OTTING William Harvey Research Institute School of Medicine and Dentistry St. Bartholomew’s and Royal London London UK [email protected] S TEFAN -M ARTIN B RAND -H ERRMANN Leibniz-Institut für Arterioskleroseforschung Universität Münster Münster Germany [email protected] M ICHAEL B RÄU Abteilung Anaesthesiologie und Operative Intensivmedizin Justus-Liebig-Universität Gießen Germany [email protected] M ATTHEW D. B REYER Division of Nephrology Medical Center, Vanderbilt University Nashville, TN USA [email protected] R ICHARD M. B REYER Division of Nephrology Medical Center, Vanderbilt University Nashville, TN USA [email protected] J ÜRGEN B ROCKMÖLLER Zentrum Pharmakologie und Toxikologie Georg-August-Universität Göttingen Göttingen Germany [email protected] M ATTHEW D. B ROWN Department of Pathology, Brigham and Women’s Hospital Harvard Medical School Boston, MA USA E DWARD M. B ROWN Division of Endocrinology, Diabetes and Hypertension Brigham and Women’s Hospital Boston, MA USA [email protected] E REZ M. B UBLIL Department of Biological Regulation The Weizmann Institute of Science Rehovot Israel [email protected]

xi

F RED B UNZ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine Baltimore, MD USA [email protected] R ÉMY B URCELIN Institute of Molecular Medicine INSERM, IFR 31 Université Paul Sabatier Toulouse France [email protected] G EOFFREY B URNSTOCK Autonomic Neuroscience Centre Royal Free and University College Medical School London UK [email protected] A MAN U. B UZDAR Department of Breast Medical Oncology The University of Texas, M.D. Anderson Cancer Center Houston, TX USA [email protected] PATRICE D. C ANI Institute of Molecular Medicine INSERM, IFR 31 Université Paul Sabatier Toulouse France PATRICK J. C ASEY Duke University Medical Center Durham, NC USA [email protected] TAMARA C ASTANEDA Department of Psychiatry Obesity Research Center, University of Cincinnati Cincinnati, OH USA [email protected] T HOMAS K. H. C HANG Faculty of Pharmaceutical Sciences The University of British Columbia Vancouver, BC Canada [email protected] D I C HEN ANZAC Research Institute The University of Rochester NY, USA B ENJAMIN N. R. C HEYETTE University of California San Francisco, CA USA [email protected]

xii

List of Contributors

R USSELL C OMPTON School of Biosciences The University of Birmingham UK [email protected]

H OLGER J. D OEGE Eli Lilly & Company, Intergrative Biology Greenfield, IN 46140 USA [email protected]

M ARGARET R. C UNNINGHAM Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde Glasgow, UK [email protected]

A NDREAS D RAGUHN Institut für Physiologie und Pathophysiologie Universität Heidelberg Heidelberg Germany [email protected]

D AVID C ZOCK Nephrology Division, Department of Internal Medicine I University Hospital Ulm Germany A NTHONY P. D AVENPORT Clinical Pharmacology Unit University of Cambridge Level 6, Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, CB2 2QQ UK [email protected] S HAHEEHAH D AWOOD Department of Breast Medical Oncology The University of Texas, M.D. Anderson Cancer Center Houston, TX USA [email protected]

C OLIN R OBERT D UNSTAN Head, Bone Research Program ANZAC Research Institute, The University of Sydney Concord, NSW Australia A NNE D URKAN Hospital for Sick Children Toronto, ONT Canada B JARKE E BERT Department of Electrophysiology Copenhagen Denmark bjeb@lundbeck com

W IM D ECLERCQ Department of Molecular Biology Ghent University Belgium

R OBERT E DWARDS Departments of Neurology and Physiology University of California at San Francisco San Francisco, CA USA [email protected]

P ETER M.T. D EEN Department of Physiology Radboud University Nijmegen Medical Center Nijmegen The Netherlands [email protected]

M ICHEL E ICHELBAUM Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology Stuttgart Germany [email protected]

V INCENZO D I M ARZO Endocannabinoid Research Group, Institute of Biomolecular Chemistry Pozzuoli Italy [email protected] M IREILLE D ELHASE Department of Pharmacology University of California San Diego, CA USA [email protected] S TEFAN D HEIN Universität Leipzig, Herzzentrum Leipzig Klinik für Herzchirurgie Leipzig Germany [email protected]

J OHN H. E XTON Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics Vanderbilt University Nashville, TN USA [email protected] S ANDRINE FAIVRE Department of Medical Oncology Beaujon University Hospital Clichy Cedex France F RANCESCO FALCIANI School of Biosciences The University of Birmingham UK [email protected]

List of Contributors

N APOLEONE F ERRARA Genentech, Inc. South San Francisco, CA USA [email protected] T HOMAS J. F EUERSTEIN Sektion Klinische Neuropharmakologie, Neurozentrum Neurochirurgische Universitätsklinik Freiburg Germany [email protected] V EIT F LOCKERZI Institut für Pharmakologie und Toxikologie Universität des Saarlandes Homburg Germany [email protected] M ARYA NN F OOTE M A Foote Associates, Westlake Village CA and Department of Microbiology Monash University Australia [email protected] U LRICH F ÖRSTERMANN Johannes Gutenberg University Mainz Germany [email protected] J ÜRGEN F RANK zet - Centre for Alternative and Complementary Methods to Animal Testing Linz Austria [email protected] J EAN -M ARIE F RERE Centre d’Ingenierie des Protéines University of Liège Liège Belgium [email protected] C HRISTIAN F REUND Protein Engineering Group Leibniz-Institute for Molecular Pharmacology Berlin Germany [email protected]

xiii

G ERD G EISSLINGER Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main Frankfurt Germany [email protected] T OM G ELDART Department of Medical Oncology Southampton General Hospital Southampton UK [email protected] N ANCY G ERITS Department of Microbiology and Virology Institute of Medical Biology, University of Tromso Tromso Norway [email protected] P IERRE G ERMAIN Department of Cell Biology and Signal Transduction Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC) Illkirch Cedex France [email protected] S TEPHEN J. G ETTING Department of Human and Health Sciences, School of Biosciences...