Table Of ContentThe Prostaglandins
PROGRESS IN RESEARCH
THE
Prostaglandins
PROGRESS IN RESEARCH
EDITED BY
PROFESSOR SULTAN M. M. KARIM
Professor and Head, Department
of Pharmacology and Therapeutics,
Makerere University Medical School,
Kampala, Uganda
MTP
Medical and Technical Publishing Co. Ltd.
Oxford and Lancaster
Copyright © 1972 MTP, Medical and Technical
Softcover reprint of the hardcover 1st edition 1972
Publishing Co Ltd
First published 1972
Published by MTP, Medical and Technical Publishing Co Ltd
Seacourt Tower
West Way
Oxford
and
St. Leonard's House
St. Leonard's Gate
Lancaster
Library of Congress Catalog Card Number: 70-172818
ISBN 978-94-010-9699-7 ISBN 978-94-010-9697-3 (eBook)
DOl 10.1007/978-94-010-9697-3
No part of this book may be
reproduced in any form without
permission from the publishers.
BY WILLMER BROTHERS LIMITED, BIRKENHEAD
Contents
General Introduction and Some Pharma-
I.
cological Actions of Prostaglandins
I
S. M. M. KARIM and K. HILLIER
2. Prostaglandins and Reproduction in
Sub-Human Primates 47
K. KIRTON
3. Prostaglandins and Human Reproduction:
Physiological Roles and Clinical Uses of
Prostaglandins in Relation to Human
Reproduction 7
I
S. M. M. KARIM
4. Cardiovascular and Renal Actions of Prosta-
glandins 165
s. M. M. KARIM and K. SOMERS
5. ERects of Prostaglandins on the Gastro-
intestinal Tract 205
A.BENNETT
6. Effects of Prostaglandins on the Respiratory
System 223
A. P. SMITH
7. Effects of Prostaglandins on Platelet Function 239
N. J. MODY
8. Prostaglandin Antagonists
K. E. EAKINS and J. H. SANNER
9. The Chemistry of the Prostaglandins 293
W P. SCHNEIDER
Index 320
v
Authors
Professor S. M. M. KARIM, Ph.D. Professor and Head, Depart
ment of Pharmacology and Therapeutics, Makerere University Medical
School, Kampala, Uganda
Dr. K. HILLIER, Ph.D. NuJfield Research OJficer, NuJfield
Department of Obstetrics and Gynaecology, Radcliffe Infirmary,
Oxford, England
Dr. K. KIRTON, Ph.D., Research Associate Fertility Research,
The Upjohn Company, Kalamazoo, Michigan, U.S.A.
Professor K. SOMERS, M.B.Ch.B., F.R.C.P., Clinical Professor,
Departmentof Medicine, Makerere University Medical School, Kampala,
Uganda
Dr. A. BENNETT, Ph.D., Senior Lecturer in Basic Science, Kings'
College Hospital Medical School, London, England
Dr. A. P. SMITH, M.B., M.R.C.P., Lecturer, Pulmonary
Research Unit, Kings College Hospital, London, England
Dr. N. J. MODY, M.B.B.S., M.D., Senior Lecturer, Clinical Bio
chemistry, Department of Biochemistry, Makerere University Medical
School, Kampala, Uganda
Dr. K. EAKINS, Ph.D., Department of Ophthalmology Research,
College of Physicians and Surgeons, Columbia University, New York,
U.S.A.
Dr. J. SANNER, Ph.D., Department of Pharmacology, Division of
Biological Research, G. D. Searle and Company, Chicago, U.S.A.
Dr. W. P. SCHNEIDER, Ph.D., Experimental Chemistry Research,
The Upjohn Company, Kalamazoo, Michigan, U.S.A.
VI
Preface
The voluminous literature on prostaglandins includes some
excellent reviews. For some time however, there has been a
need for the collection in one volume of information from
individual experts actively engaged in different aspects of
prostaglandin research. This book is an attempt to fulfil that
need. In view of the expanding interest and ever-growing
accumulation of data of the various effects of prostaglandins it
is hoped to revise the book and bring it up-to-date periodically.
The largest section is that on reproduction, in which field
progress in research and clinical applications thereof have been,
and are, of great significance particularly in the area of popula
tion control. This is not to decry the skill and efforts of investi
gators in other aspects of prostaglandin activity nor the potential
biological or therapeutic importance of their findings. In this
context, what may appear to be omissions are individual
sections on prostaglandin activity in the central nervous system,
in the eye and as mediators of the inflammatory response.
These are considered in the chapter on General Pharmacology
of the Prostaglandins not because they might be considered to
be of lesser impact and significance but in order to achieve a
rapid publication of the book.
S. M. M. KARIM
Kampala, Uganda. January 1972.
Acknowledgements
Tables and Figures previously published are, in general,
acknowledged by the reference in the legends and I am
grateful to the authors, editors and publishers for their per
mission.
Vll
Vlll Acknowledgements
My thanks are due to Mrs. Kanta Peshavaria, Mrs. Celia
Flory and K. M. F. Jaffer for cross-checking the journal
references and for their assistance with proof reading. The
index was prepared by Mr. Jim Welluang at a very short notice.
I am very grateful to Dr. Donald MacIntosh for advice, help
and encouragement and to the publishers, particularly
D. G. T. Bloomer, for their co-operation in achieving rapid
publication.
CHAPTER 1
General Introduction and Some
Pharmacological Actions of Prostaglandins
SULTAN M. M. KARIM
Professor and Head,
Department of Pharmacology and Therapeutics,
Makerere University Medical School,
Kampala, Uganda
and
KEITH HILLIER
Nujfield Research Ojficer,
Nujfield Department if Obstetrics and Gynaecology,
Radcliffe Ir!/irmary,
Oxford, England
I. I. Historical survey
1.2. Isolation, purification and chemical structures
1.3. Occurrence and release of prostaglandins
1.4. Fate and metabolism
1.5. Extraction and purification of prostaglandins
1.6. Methods for quantitative analysis of p."ostaglandins
1.6. I. Bioassay
1.6.2. Spectrophotometric method
1.6.3. Enzymatic analysis
1.6+ Gas-liquid chromatography with flame ionisation detector
1.6.5. Gas-liquid chromatography with electron capture detector
1.6.6. Gas-liquid chromatography with mass spectometry
1.7. Prostaglandins and smooth muscle
1.7.1. The action of prostaglandins upon smooth muscle
I. 7. 2. Ion dependence of prostaglandin response
1.7.3. Mechanism of action
1.8. Metabolic effects of prostaglandins
1.8. I. In vitro studies
1.8.2. In vivo studies
1.8.3. Cyclic A.M.P.
1.g. Central nervous system
1.10. Prostaglandins and the eye
1.1 I. Prostaglandins and anti-inflammatory drugs
References
1.1. Historical Survey
The prostaglandins are a family of closely related unsaturated
hydroxy fatty acids. They were first found in male accessory
glands and their secretions and are now known to occur with
widespread distribution in animal and human tissues and body
fluids. The term 'Prostaglandin' was coined by von Euler
(I 935a) in the belief that the biologically active substance found
in human semen was a secretion of the prostate gland.
The presence of biological activity in extracts of prostate
gland and its secretions was recognised by scientists in the early
part of the present century. Japelli and Scafa (1906) observed a
rise in the blood pressure of the dog upon injecting extracts of
bull and dog prostate glands. A few years later Battez and
Boulet (1913) showed a fall in the blood pressure in the dog
when aqueous extracts of human prostate were injected.
Whether the biological activity present in these extracts was
due to the prostaglandins or due to some other substances is
not known.
The first definite reference to the existence of what is now
known as prostaglandins was made by Kurzrok and Lieb in
1930. These North American scientists showed that fresh
human semen could either inhibit or stimulate the motility of
the human uterus in vitro. The response was to some extent
dependent upon the proven fertility or long standing sterility of
the woman from whom the uterine strips were obtained.
A few years after the studies of Kurzrok and Lieb, two Euro
pean scientists (von Euler in Sweden and Goldblatt in England)
independently observed and studied the marked smooth muscle
stimulating activity of human seminal fluid (Euler 1934, 1935
(a) (b); Goldblatt 1933, 1935). Von Euler demonstrated similar
activity in the seminal fluid of the monkey, sheep, goat and in
extracts of sheep seminal vesicles. All these extracts had two
main biological properties; that of stimulating smooth muscle
and of lowering arterial blood pressure in experimental animals.
Subsequently von Euler showed that the biological activity of
the seminal fluid was associated with a fraction containing lipid
soluble acids. Von Euler's studies clearly showed that the
