The Prostaglandins: Volume 2

356 Pages·1974·10.512 MB·English

by  Peter W. Ramwell (auth.)

THE PROSTAGLANDINS
VOLUME 2
A Continuation Order Plan is available for this series. A continuation order will bring
delivery of each new volume immediately upon publication. Volumes are billed only upon
actual shipment. For further information please contact the publisher.
THE
PROSTAGLANDINS
VOLUME 2
Edited by Peter W. Ramwell
Department of Physiology and Biophysics
School of Medicine
Georgetown University
Washington, D. C.
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Ramwell, Peter W
The prostaglandins.
Includes bibliographies.
1. Prostaglandins. I. Title. [DNLM: 1. Prostaglandins. QU90 R184pj
QP80l.P68R95 612'.405 72-76858
ISBN-13: 978-1-4613-4546-6 e-ISBN-13: 978-1-4613-4544-2
DOl: 10.1007/978-1-4613-4544-2
© 1974 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1974
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
United Kingdom edition published by Plenum Press, London
A Division of Plenum Publishing Company, Ltd.
4a Lower John Street, London, WIR 3PD, England
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Contributors
NIELS H. ANDERSEN DONALD E. MACFARLANE
Department of Chemistry Specialized Center for Thrombosis Research
University of Washington Health Sciences Center
Seattle , Washington Temple University
Philadelphia. Pennsylvania
HENRY R. BOURNE
Division of Clinical Pharmacology
MARY ANN MARRAZZI
University of California Medical Center
San Francisco, California Department of Pharmacology
School of Medicine
P. F. EAST Washington University
St. Louis, Missouri
Searle Laboratories Inc.
Chicago, Illinois
KEITH MASHITER
S. H. FERREIRA
Clinical Research Unit
Wellcome Research Laboratories
and
Langley Court
Department of Medicine
Beckenham, Kent, England
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
JAMES B. FIELD
Clinical Research Unit
R. A. MUELLER
and
Department of Medicine Searle Laboratories Inc.
University of Pittsburgh School of Medicine Chicago, Illinois
Pittsburgh, Pennsylvania
MALCOLM JOHNSON T. V. N. PERSAUD
Department of Physiology and Biophysics Teratology Research Laboratory
School of Medicine Department of Anatomy
Georgetown University University of Manitoba
Washington, D.C. Winnipeg, Canada
W. J. POTTS J. R. VANE
Searle Laboratories Inc. Wellcome Research Laboratories
Chicago, lllinois Langley Court
Beckenham, Kent, England
J. BRYAN SMITH
Cardeza Foundation BERNARDO BORIS V ARGAFTIG
and
Merrell International Research Center
Department of Pharmacology
Strasbourg, France
Thomas Jefferson University
Philadelphia, Pennsylvania
Contents
Chapter 1
Aspirin and Prostaglandins
S. H. Ferreira and J. R. Vane
I. Introduction 1
II. Inhibition of Prostaglandin Synthetase from Different
Species and Tissues by Nonsteroid Anti-Inflammatory
Agents 3
A. Absolute Potencies 5
B. Relative Potencies 5
III. Relationship between Potency of Aspirin-Like Drugs
Against Prostaglandin Synthetases In Vitro and
Anti-Inflammatory Activity 7
A. Variations in Potency 7
B. Drug Concentrations in Plasma 9
IV. Contribution of Prostaglandins to the Inflammatory
Process 12
A. Prostaglandin Release 12
B. Release of Chemical Mediators 13
C. Possible Control Mechanisms for Prostaglandin Bio-
synthesis and Release 15
D. Inflammatory Effects of Prostaglandins 18
V. Relationship between In Vivo Inhibition of Prostaglandin
Generation and Therapeutic Effects of Nonsteroid
Anti-Inflammatory Drugs 23
VI. Side-Effects of Nonsteroid Anti-Inflammatory Agents 25
vii
Contents
VII. Use of Nonsteroid Anti-Inflammatory Drugs as a Test for
the Involvement of Prostaglandins in Some Biological
Systems 27
A. Intestinal Smooth Muscle Tone 27
B. Contractions of the Uterus 30
C. Contribution of Prostaglandins to Ovary Function 32
D. Control of Lipolysis 32
E. Control of Release of the Sympathetic Mediator 33
F. Local Regulation of Blood Flow 34
VIII. Conclusions 38
IX. References 39
Chapter 2
The Thyroid Gland
Keith Mashiter and James B. Field
I. Introduction 49
II. Occurrence and Synthesis of Prostaglandins in the Thyroid 50
A. Normal Thyroid 50
B. Medullary Carcinoma of the Thyroid 50
C. Prostaglandin Synthesis in the Thyroid 51
III. Effects of Prostaglandins on Thyroid Gland Metabolism 52
A. The Adenylate Cyclase-Cyclic AMP System 52
B. Iodine Metabolism and Thyroid Hormone Secretion 56
C. Glucose Oxidation 58
D. Incorporation into Phospholipid 61
32p
E. Conclusions 62
IV. Interrelationships of Prostaglandins and TSH 62
A. Prostaglandin Analogues 63
B. Combined Actions of Prostaglandins and TSH 64
C. Dissociation of TSH and Prostaglandin Effects 68
D. Conclusions 69
V. Summary 70
VI. References 70
Chapter 3
The Mature Erythrocyte
Malcolm Johnson
I. Introduction 75
II. Prostaglandins in the Erythrocyte 76
viii
Contents
A. Synthesis and Release 76
B. Metabolism and Inactivation 76
C. Binding 77
D. Uptake and Distribution 77
III. Action on the Mechanical Properties of the Red Cell 77
A. Deformability 77
B. Hemolysis 80
IV. Effects on Obligatory Cation Exchange 81
A. Monovalent Cations 81
B. Divalent Cations 81
V. Metabolic Effects of Prostaglandins 84
A. ATP and AT P-Regulating Enzymes 84
B. Cyclic AMP 87
VI. Effects on Hemoglobin 89
VII. Implications in the Pathological State 91
VIII. Prostaglandin Antagonists 93
IX. Use of Prostaglandins in Preparation and Storage of Plasma
Concentrates 94
X. Conclusions 94
XI. References 95
Chapter 4
Prostaglandin Dehydrogenase
Mary Ann Marrazzi and Neils H. Andersen
I. Introduction 99
II. Metabolic Deactivation 101
III. PGDH Distribution 103
IV. Enzyme Purification 106
A. Requirements 10 6
B. Methods 106
C. Assays for PGDH Activity 109
V. Some Properties of the Purified PGDH 111
A. Purity 111
B. Stability 112
C. Molecular Weight 112
D. pH 112
E. Coenzyme 113
F. Substrate Activity 114
VI. Characteristics of Binding to PGDH 116
A. The PG Site 116
ix