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Radioimmunoassay in Basic and Clinical Pharmacology PDF

624 Pages·1987·16.356 MB·English
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Handbook of Experimental Pharmacology Volume 82 Editorial Board G.y' R. Born, London P. Cuatrecasas, Research Triangle Park, NC H. Herken, Berlin A. Schwartz, Cincinnati, OH Radioimmunoassay in Basic and Clinical Pharmacology Contributors L. Bartalena· K. Brune' F. Celada . I. Christens son-Nylander G. Ciabattoni . D. Cocchi· M. G. Currie' 1 Dawes' F. Dray E. Ezan . D. M. Geller' 1 Grassi . V. Guardabasso . E. C. Hayes E. Knoll· G. A. Limjuco . 1 Mac1ouf· S. Mamas' S. Mariotti M.L. Michener' P.I Munson' M.G. Murphy' P. Needleman G. Nilsson' F. Nyberg' C.W. Parker' C. Patrono . M. Pazzagli D. S. Pepper' B.A. Peskar . B. M. Peskar . A. Pinchera P. Pradelles . M. Reinke' D. Rodbard . C. Rougeot . D. Schwartz M. Serio . Th. Simmet . S. Spector' L. Terenius . L. E. Underwood lH.Walsh· H.Wisser· H.C.Wong· R.S.Yalow· H.I Zweerink Editors C. Patrono and B.A. Peskar Springer-Verlag Berlin Heidelberg New York London Paris Tokyo CARLO PATRONO, Professor of Molecular Pharmacology Institute of Pharmacology Catholic University of the Sacred Heart Largo Francesco Vito, 1 1-00168 Rome BERNHARD A. PESKAR, Professor of Pharmacology and Toxicology Institute of Pharmacology and Toxicology Ruhr-University Bochum 1m Lottental, P.O. Box 102148 D-4630 Bochum 1 With 129 Figures Library of Congress Cataloging-in-Publication Data. Radioimmunoassay in basic and clinical pharmacology. (Handbook of experimental pharmacology; v. 82) Includes index. 1. Radioimmunoassay. 2. Biomolecules -Analysis. 3. Drugs-Analysis. I. Bartalena, L. II. Patrono, Carlo, 1944- . III. Peskar, B. A. (Bernhard A.) IV. Series. [DNLM: 1. Hormones-analysis. 2. Peptides-analysis. 3. Radioimmunoassay. WI HA51L v.82/QW 570 R1294] QP905.H3 vol. 82 615'.1 s 87-9659 [QP519.9.R3] [615'.1901] ISBN-13: 978-3-642-71811-3 e-ISBN-13: 978-3-642-71809-0 DOl: 10.1007/978-3-642-71809-0 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, re-use 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 version ofJune 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1987 Sofkover reprint of the hardcover I st edition 1987 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 publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. 2122/3130-543210 List of Contributors L. BARTALENA, Istituto di Metodologia Clinica e Medicina del Lavoro, Cattedra di Endocrinologia e Medicina Costituzionale, Universita degli Studi di Pisa, Viale del Tirreno, 64, 1-56018 Tirrenia (Pisa) K. BRUNE, Institut fUr Pharmakologie und Toxikologie, Universitat Erlangen Niirnberg, Universitatsstr.22, D-8520 Erlangen F. CELADA, Cattedra di Immunologia dell'Universita degli Studi di Genova, Viale Benedetto XV, 10, 1-16132 Genova I. CHRISTENSSON-NYLANDER, Department of Pharmacology, University of Uppsala, Box 591, S-75124 Uppsala G. CIABATTONI, Istituto di Farmacologia, Universita Cattolica del Sacro Cuore, Facolta di Medicina e Chirurgia "Agostino Gemelli", Largo Francesco Vito, 1, 1-00168 Roma D. COCCHI, Universita degli Studi di Milano, Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica, Via Vanvitelli, 32, 1-20129 Milano M. G. CURRIE, Medical University of South Carolina, Department of Pharma cology, 171 Ashley Ave., Charleston, SC 29425, USA J. DAWES, MRCjScottish National Blood Transfusion Service, Blood Compo nents Assay Group, 2 Forrest Road, Edinburgh EH1 2QW, Great Britain F. DRAY, U207, INSERM, Institut Pasteur, Unite de Radioimmunologie Analytique, 28, rue du Docteur Roux, F-75724 Paris Cedex 15 E. EZAN, U207, INSERM, Institut Pasteur, Unite de Radioimmunologie Ana lytique, 28, rue du Docteur Roux, F-75724 Paris Cedex 15 D. M. GELLER, Washington University School of Medicine, The Edward Ma linckrodt Department of Pharmacology, Box 8103, 660 South Euclid Ave., St. Louis, MO 63110, USA J. GRASSI, Section de Pharmacologie et d'lmmunologie, Laboratoire d' Etudes Radioimmunologiques, CEA, Departement de Biologie CEN-Saclay, F-91191 Gif sur Yvette Cedex V. GUARDABASSO, Istituto di Ricerche Farmacologiche "Mario Negri", Via Eritrea, 62, 1-20157 Milano VI List of Contributors E. C. HAYES, Immunology Research, Merck Sharp & Dohme Research Labora tories, P.O. Box 2000, Rahway, NJ 07065-0900, USA E. KNOLL, Abteilung fUr Klinische Chemie, Robert-Bosch-Krankenhaus, Auer bachstr.ll0, D-7000 Stuttgart 50 G. A. LIMJUCO, Immunology Research, Merck Sharp & Dohme Research Labo ratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA J. MACLOUF, U 150, INSERM - LA334 CNRS, H6pital Lariboisiere, 6 rue Guy Patin, F-75475 Paris Cedex 10 S. MAMAS, U207, INSERM, Institut Pasteur, Unite de Radioimmunologie Ana lytique, 28, rue du Docteur Roux, F-75724 Paris Cedex 15 S. MARIOTTI, Istituto di Metodologia Clinica e Medicina del Lavoro, Cattedra di Endocrinologia e Medicina Costituzionale, Universita degli Studi di Pisa, Viale del Tirreno, 64, 1-56018 Tirrenia (Pisa) M. L. MICHENER, Washington University School of Medicine, The Edward Malinckrodt Department of Pharmacology, Box 8103, 660 South Euclid Ave., St. Louis, MO 63110, USA P. J. MUNSON, Laboratory of Theoretical and Physical Biology, National Insti tute of Child Health and Human Development, National Institutes of Health, Building 10, Room 8C312, Bethesda, MD 20892, USA M. G. MURPHY, Department of Pediatrics, Division of Endocrinology, The U ni versity of North Carolina at Chapel Hill, Clinical Sciences Building 229H, Chapel Hill, NC 27514, USA P. NEEDLEMAN, Washington University School of Medicine, The Edward Ma linckrodt Department of Pharmacology, Box 8103, 660 South Euclid Ave., St. Louis, MO 63110, USA G. NILSSON, Department of Physiology, Faculty of Veterinary Medicine, The Swedish University of Agricultural Sciences, P.O. Box 7045, S-75007 Uppsala 7 F. NYBERG, Department of Pharmacology, University of Uppsala, Box 591, S-75124 Uppsala C. W. PARKER, Department of Internal Medicine, Division of Allergy and Im munology, Washington University School of Medicine, Box 8122, 660 South Euclid Ave., St. Louis, MO 63110, USA C. PATRONO, Istituto di Farmacologia, Universita Cattolica del Sacro Cuore, Facolta di Medicina e Chirurgia "Agostino Gemelli", Largo Francesco Vito, 1, 1-00168 Roma M. PAZZAGLI, Dipartimento di Fisiopatologia Clinica, Unita di Endocrinologia, Universita degli Studi di Firenze, Viale Morgagni, 85, 1-50135 Firenze D. S. PEPPER, Scottish National Blood Transfusion Service, Headquarters Unit Laboratory, 2 Forrest Road, Edinburgh EH1 2QN, Scotland, Great Britain List of Contributors VII B. A. PESKAR, Institut fUr Pharmakologie und Toxikologie, Ruhr-Universitat Bochum, 1m Lottental, D-4630 Bochum 1 B. M. PESKAR, Abteilung fUr Experimentelle Klinische Medizin, Ruhr-Universitat Bochum, 1m Lottental, D-4630 Bochum 1 A. PINCHERA, Istituto di Metodologia Clinica e Medicina del Lavoro, Cattedra di Endocrinologia e Medicina Costituzionale, Universita degli Studi di Pisa, Viale del Tirreno, 64, 1-56018 Tirrenia (Pisa) P. PRADELLES, Section de Pharmacologie et d'lmmunologie, Laboratoire d'Etudes Radioimmunologiques CEA, Departement de Biologie CEN-Saclay, F-91191 Gif sur Yvette Cedex M. REINKE, Institut fUr Pharmakologie und Toxikologie, Universitat Erlangen Niirnberg, Universitatsstr.22, D-8520 Erlangen D. RODBARD, Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 8C312, Bethesda, MD 20892, USA C. ROUGEOT, U207, INSERM, Institut Pasteur, Unite de Radioimmunologie Analytique, 28, rue du Docteur Roux, F-75724 Paris Cedex 15 D. SCHWARTZ, Washington University School of Medicine, The Edward Malinckrodt Department of Pharmacology, Box 8103, 660 South Euclid Ave., St. Louis, MO 63110, USA M. SERIO, Dipartimento di Fisiopatologia Clinica, Unita di Endocrinologia, Universita degli Studi di Firenze, Viale Morgagni, 85, 1-50135 Firenze TH. SIMMET, Institut fUr Pharmakologie und Toxikologie, Ruhr-Universitat Bochum, 1m Lottental, D-4630 Bochum 1 S. SPECTOR, Department of Neuroscience, Roche Institute of Molecular Biology, Roche Research Center, Building 102, Nutley, NJ 07110, USA L. TERENIUS, Department of Pharmacology, University of Uppsala, Box 591, S-75124 Uppsala L. E. UNDERWOOD, Department of Pediatrics, School of Medicine, Division of Endocrinology, The University of North Carolina at Chapel Hill, Clinical Sciences Building 229H, Chapel Hill, NC 27514, USA J. H. WALSH, Center for Ulcer Research and Education, Veterans Administration Wadsworth, Wilshire and Sawtelle Bvds., Building 115, Room 115, Los Angeles, CA 90073, USA H. WISSER, Abteilung fUr Klinische Chemie, Robert-Bosch-Krankenhaus, Auer bachstr.ll0, D-7000 Stuttgart 50 VIII List of Contributors H. C. WONG, Department of Medicine, University of California, Los Angeles, CA 90024, USA R. S. YALOW, Solomon A. Berson Research Laboratory, Veterans Administration Medical Center, 130, West Kingsbridge Road, Bronx, NY 10468, USA H. J. ZWEERINK, Immunology Research, Merck Sharp & Dohme Research Labo ratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA Preface Thirty years have elapsed since the first description by S. A. BERSON and R. S. Y ALOW of the basic principles of radioimmunoassay (RIA). During this period of time, RIA methodology has been instrumental to the growth of many areas of biomedical research, including endocrinology, oncology, hematology, and pharmacology. It has done so by providing a relatively simple universal tool allowing, for the first time, the detection of endogenous mediators that are present in body fluids at concentrations as low as 10-12_10-10 M. The fundamental nature of this discovery and the wide-ranging fall-out of basic and clinical knowledge derived from its application have been acknowledged by the many honors tributed to its pioneers, including the Nobel Prize awarded to Dr. Y ALOW 10 years ago. Although several excellent books have been published during the past decades covering various aspects of RIA methodology, we felt the need, as pharmacologists, for a comprehensive discussion of the methodological and conceptual issues related to the main classes of mediators of drug action and to drugs themselves. Thus, we gladly accepted the challenge provided by the invitation to edit a volume of the Handbook of Experimental Pharmacology on Radioimmunoassay in Basic and Clinical Pharmacology. We tried to balance the emphasis placed on more general aspects of the RIA methodology and that on specific mediators. A potentially endless list of substances of pharmacological interest was necessarily limited by considerations of space and general interest, although we did make some last-minute adjustments in order to include very recent and exciting developments. A number of introductory chapters provide the reader unfamiliar with RIA with all the basic information concerning the production and characterization of antibodies, labeling techniques, statistical aspects, and validation criteria. Moreover, each of these chapters provides the experienced reader with further insight into problems related to the development and validation of RIA for newly discovered mediator(s). In the following chapters, the emphasis is placed on the technical details relevant to each class of compounds and on specific aspects of their application to basic and/or clinical pharmacological studies. New develop ments in this area such as monoclonal antibodies and nonradioactive labeling techniques are also given adequate coverage. We hope this book will represent a valuable working instrument in the hands of those investigators interested in measuring changes in the synthesis and metabolism of a variety of endogenous mediators, as well as in the kinetics of x Preface drugs, as related to experimental or clinical models of disease and to pharma cological intervention. We are indebted to Mrs. P. TIERNEY, Mrs. A. ZAMPINI, and Ms. K. BUSCHEY for invaluable help in the handling and editing of the manuscripts, to Mrs. D. M. WALKER for providing all the necessary support and advice from the publisher, and to all the authors for generously sharing with us the effort and time that this project required. Rome C. PATRONO Bochum B.A. PESKAR Contents CHAPTER 1 Radioimmunoassay: Historical Aspects and General Considerations R. S. Y ALOW. With 1 Figure . . . 1 A. Historical Aspects. . . . . . 1 B. Principle, Practices, and Pitfalls 1 I. Principle 2 II. Practices 2 III. Pitfalls . 4 C. Conclusions 5 References. . 5 CHAPTER 2 Basic Principles of Antigen-Antibody Interaction F. CELADA. With 4 Figures . . . . . 7 A. Introduction to the Immune System 7 B. Antigens. . . . . . . . . . . . 10 I. Chemical Nature . . . . . . 10 II. Antigenic Determinants (Epitopes) . 11 III. Haptens and Carriers . . . . . . 11 IV. Size of Determinants. . . . . . . 11 V. Sequential and Conformational Epitopes 11 C. Antibodies . . . . . . . . . . . . . 12 I. The Ab Combining Site (Paratope) 13 D. The Immune Interaction . 14 I. The Forces Involved. 14 II. Paratope-Epitope Fit. 15 III. Specificity . . . . . 16 IV. Affinity . . . . . . 16 E. Effects of Ab-Ag Interaction 19 I. Free Ag Binds Ig Receptor 19 II. Free Ag Binds Free Ab 19 III. Free Ab Binds Cell-Associated Ag . 20 F. Immune Interaction as a Signal: Role of Conformational Changes 20 I. Antibody. 20 II. Antigen 21 References. . . . 21

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