Radioimmunoassay in Basic and Clinical Pharmacology

624 Pages·1987·16.356 MB·English

by  R. S. Yalow (auth.), Carlo Patrono, Bernhard A. Peskar (eds.)

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
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© Springer-Verlag Berlin Heidelberg 1987
Sofkover reprint of the hardcover I st edition 1987
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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