Prostaglandins and Thromboxanes

442 Pages·1977·10.25 MB·English

by  Elisabeth Granström (auth.), F. Berti, B. Samuelsson, G. P. Velo (eds.)

Prostaglandins
and Thromboxanes
NA.TO ADVANCED STUDY INSTITUTES SERIES
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Prostaglandins
and Thromboxanes
Edited by
F. Berti
University of Milan
Milan, Italy
B. Samuelsson
Karolinska Institute
Stockholm, Sweden
and
G. P. Velo
University of Padua
Verona, Italy
PLENUM PRESS. NEW YORK AND LONDON
Published in cooperation with NATO Scientific Affairs Division
Library of Congress Cataloging in Publication Data
Nato Advanced Study Institute on Advances in Prostaglandins, Erice, Italy, 1976.
Prostaglandins and thromboxanes.
(Nato advanced study institutes series: Series A, Life Sciences; v. 13)
Includes index.
1. Prostaglandins-Congresses. 2. Thromboxanes-Congresses. I. Berti, Ferruccio.
II. Samuelsson, Bengt. III. Velo, G. P. IV. Title. V. Series.
QP801.P68N371976 591.1'924 77-5364
ISBN-13: 978-1-4684-2780-6 e-ISBN-13: 978-1-4684-2778-3
001: 10.1007/978-1-4684-2778-3
Lectures presented at the NATO Advanced Study Institute on Advances in
Prostaglandins held in the "Ettore Majorana" Center in Erice, Sicily,
October 4-15, 1976
© 1977 Plenum Press, New York
Softcover reprint of the hardcover I st edition 1977
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
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
PREFACE
This volume presents lecture notes from the session
of the International School of Pharmacology, at the
"Ettore Majorana" Centre, on Advances in Prostaglandins
that took place in Erice (Sicily), October 4 to October
15, 1976. The School was a NATO Advanced Study Institute.
The aim of this international course was a compre
hensive discussion by experts in various disciplines of
the present status of our knowledge of the biological
role of prostaglandins and thromboxanes.
The synthesis, metabolism, and function of prosta
glandins have been evaluated at the cellular level, in
isolated tissues, and/or in the intact organism. The
mode of action of prostaglandins and their interactions,
particularly with cyclic nucleotides, in normal and
pathological conditions, has been discussed with the
aim of understanding the possible role of these compounds
in hormonal regulation and cell response.
The prostaglandin biosynthetic capacity of different
tissues, under various experimental conditions, in the
presence of specific precursors, and the inhibitory ac
tivity of different agents have been examined to ascer
tain the relationship between function and metabolism.
For these reasons the discussion has also been
extended to the methods (biological, immunological, and
spectrometric) available for the direct and specific
determination of prostaglandins and the evaluation of
their synthesis and metabolism.
The Editors hope that the book will be useful both
to beginners and to those with a long-time interest in
prostaglandins.
F. Berti
B. Samuelsson
G. P. Velo
v
CONTENTS
Chemistry of Prostaglandins and
Thromboxanes . . 1
E. Granstrom
Some Synthetic Aspects of Prostaglandins 9
P. Crabbe
Prostaglandin Bioassay 27
S. H. Ferreira
Radioimmunoassays of Prostaglandins and
Thromboxanes . . . . . . . 41
E. Granstrom
Vapor-Phase Methods for Quantitative
Evaluation of Prostaglandins
and Related Compounds in
Biological Samples . . 53
S. Nicosia and G. Galli
Biosynthesis of Prostaglandins 65
E. Granstram
Metabolism of Prostaglandins 75
E. Granstrom
Screening for Inhibitors of Prostaglandin
and Thromboxane Biosynthesis 85
R. J. Gryglewski
Prostaglandin Synthetase Inhibitors . 111
T. Y. Shen
Respiratory System (General Introduction) 137
L. Puglisi and F. Maggi
vii
viii CONTENTS
Generation of Prostaglandin and
Thromboxane-like Substances
by Large Airways and Lung
Parenchyma . . . . . . . . . 165
R. J. Gryglewski, A. Dembinska-Kiec,
and L. Grodzinska
Clinical Effects of the Prostaglandins
on the Respiratory System 179
M. F. Cuthbert
Aspirin-Sensitive Asthma: Its Relationship
to Inhibition of Prostaglandin
Biosynthesis . . . . . . . . . . . 191
R. J. Gryglewski, A. Szczeklik,
and E. Nizankowska
Physiological Roles of Prostaglandins
in Reproduction . . . . . 205
N. L. Poyser
Clinical Use of Prostaglandins for
Termination of Pregnancy and
Induction of Labour 221
M. Bygdeman
Introduction to Circulatory System 243
F. Berti and C. Omini
Polypeptides: Vascular Actions as
Modified by Prostaglandins 251
P. Y.-K. Wong, J. C. McGiff, and
A. Terragno
Prostaglandins and Vascular Wall 265
R. J. Gryglewski
The Role of Prostaglandins in
Gastrointestinal Tone and Motility . .. 275
A. Bennett
Effect of Prostaglandins on
Gastrointestinal Functions 287
A. Robert
Antisecretory Prostaglandins and
Gastric Mucosal Erosions in
the Rat . . . . . . . . 315
B. J. R. Whittle
CONTENTS ix
The Role of Prostaglandins and
Cyclic Nucleotides in
Inflammation . . . . . 323
J. P. Giroud, G. P. Velo, and
D. A. Willoughby
Prostaglandins and Mast Cell Histamine
Release . . . . . 345
B. J. R. Whittle
Prostaglandins and Non-Steroidal
Anti-Inflammatory Drugs 353
S. H. Ferreira
Influence of Anti-Inflammatory Steroids
on Prostaglandin and Thromboxane
Release from Tissues . 363
R. J. Gryglewski, R. Korbut, and
A. Dembinska-Kiec
Influence of Prostaglandins on Central
Functions . . . . . 383
R. Fumagalli, G. C. Folco, and
D. Longiave
Prostaglandins as Modulators of Autonomic
Neuroeffector Transmission 423
P. Hedqvist
Inflammatory Pain and Fever . . . . 433
S. H. Ferreira
List of Contributors 443
Index . 447
CHEMISTRY OF PROSTAGLANDINS AND THROMBOXANES
Elisabeth Granstrom
Dept. of Chemistry, Karolinska Institutet
S-104 01 Stockholm 60, Sweden
The structures of several prostaglandins were determined during
the early 1960#s. First, two biologically active compounds were iso
lated from sheep vesicular glands; these compounds were called PGEl
and PGFla (for a review, see Ref. 1). Reduction of PGEl with sodium
borohydride gave a mixture of two epimeric compounds, PGFla and PGF1S'
Further studies on the structures of these compounds revealed that
they were derivatives of a C20 carboxylic acid, later named prosta
.noic acid, which contained a five-membered ring (C-a to C-12) with
two side chanis. Prostaglandins of the E type were shown to have a
keto group at C-9, whereas a hydroxyl group was found in this posi
tion in the F prostaglandins. The index a or S indicates the stereo
chemical position of this hydroxyl group. Common to all these prosta
glandins and most others is the presence of an L-hydroxyl group at
C-15 and a ~13_trans double bond.
The different classes of prostaglandins are further subgrouped
according to the degree of saturation, and an index indicates the
number of double bonds. Prostaglandins of the "1" type contain
only the t 13-trans double bond, PG2 contains also a ~5-cis double
bond, and PG3 an additional ~17-cis double bond. Thus PGE2 e.g. is
lla,15-dihydroxy-9-ketoprost-5(cis),13(trans)-dienoic acid.
PGE1, E2, E3, Fla, F2a and F3a were called the "primary" prosta
glandins, and all except PGF3a were also identified in human seminal
plasma. From this source were later isolated eight additional prosta
glandins. These were all dehydrated prostaglandins, formed by loss
of the lla hydroxyl group from a PGE compound, which resulted in
the formation of a double bond either in the ~10 position (PGA com-
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