Pharmacology of the Skin I: Pharmacology of Skin Systems Autocoids in Normal and Inflamed Skin

526 Pages·1989·11.94 MB·English

by  E. Christophers

Handbook of
Experimental Pharmacology
Volume 871/
Editorial Board
G.v. R. Born, London
P. Cuatrecasas, Research Triangle Park, NC
H. Herken, Berlin
A. Schwartz, Cincinnati, OH
Pharmacology
of the Skin I
Pharmacology of Skin Systems
Autocoids in Normal and Inflamed Skin
Contributors
D. I. Abramson, J. C. Allen, H. P. Baden, R. C. Benyon, A. G. Bird,
S. D. Brain, K. A. Brown, E. Christophers, M. K. Church, L. S. Clegg,
K.1. Collins, W. I. Cranston, R. P. R. Dawber, D. C. Dumonde,
c.J.
Dunn, 1. A. Edwardson, V. Eisen, B. A. Ellis, 1. C. Foreman,
M.1. Forrest, M. Goos, M. W. Greaves, S. T. Holgate, V. K. Hopsu-Havu,
A. B. Kay, C. M. Lapiere, F. Lawlor, B. Lynn, P. Mauvais-Jarvis, 1. Morley,
B. V. Nusgens, E. M. Saihan, C. Schubert, S. Shuster, A. 1. Thody, G. Volden,
A. 1. Wardlaw, S. I. Wasserman, T. 1. Williams, D. A. Willoughby, F. Wright,
M. A. Zar, V. A. Ziboh
Editors
Malcolm W. Greaves and Sam Shuster
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Professor MALCOLM W. GREAVES, M.D., Ph.D., F.R.C.P.
The Institute of Dermatology
St. Thomas's Hospital
Lambeth Palace Road
London SEl 7EH
Great Britain
Professor SAM SHUSTER, M.D., F.R.C.P.
The University of Newcastle upon Tyne
Department of Dermatology
The Royal Victoria Infirmary
Newcastle upon Tyne NEl 4LP
Great Britain
With 78 Figures
ISBN-13: 978-3-642-73799-2 e-ISBN -13: 978-3-642-73797-8
DOl: 10.1007/978-3-642-73797-8
Library of Congress Cataloging in Publication Data. Pharmacology of the skin/contributors, D. I. Abramson ... let al.);
editors, M. W. Greaves and S. Shuster. p. cm. - (Handbook of experimental pharmacology; v. 87/1-2) Includes
index. (v. 1: alk. paper).!. Dermatopharmacology. 2. Skin-Physiology. I. Abramson, David I.
(David Irvin), 1905- . II. Greaves, M. W. III. Shuster, Sam. IV. Series. [DNLM: 1. Dermatologic Agents
pharmacology. 2. Skin-drug effects. 3. Skin Diseases-drug therapy. WI HA51L v.87 pt. 1-2/QV 60 P536]
QP905.H3 vol. 87/1-2 [RM303] 615'.1 s-dcl9 [615'.778] DNLM/DLC for Library of Congress
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List of Contributors
D.1. ABRAMSON, 916 North Oak Avenue, Oak Park, IL 60302, USA
J. C. ALLEN, Research Division, The North East Wales Institute, Kelsterton
College, Connah's Quay, Deeside, Clwyd CH54BR, Great Britain
H. P. BADEN, Harvard Medical School, Department of Dermatology, Massa
chusetts General Hospital, 32, Fruit Street, Boston, MA 02114, USA
R. C. BENYON, Clinical Pharmacology, University of Southampton, Southamp
ton General Hospital, Tremona Road, Southampton S09 4XY, Great Britain
A. G. BIRD, Regional Immunology Department, Newcastle General Hospital,
Westgate Road, Newcastle upon Tyne NE1 6BE, Great Britain
S. D. BRAIN, Clinical Research Centre, Section of Vascular Biology, Watford
Road, Harrow, Middlesex HA1 3UJ, Great Britain
K. A. BROWN, Department of Immunology, St. Thomas's Hospital, Lambeth
Palace Road, London SE1 7EH, Great Britain
E. CHRISTOPHERS, Department of Dermatology, Hautklinik, Christian-Albrechts
Universitat, Schittenhelmstr.7, D-2300 Kiel
M. K. CHURCH, Clinical Pharmacology, University of Southampton, Southamp
ton General Hospital, Tremona Road, Southampton S09 4XY, Great Britain
L. S. CLEGG, Clinical Pharmacology, University of Southampton, Southampton
General Hospital, Tremona Road, Southampton S094XY, Great Britain
K. J. COLLINS, Medical Research Council, Environmental Physiology Unit,
(Annexe), 242, Pentonville Road, London NE1 9LB, Great Britain
W. I. CRANSTON, Department of Medicine, St. Thomas's Hospital, Medical
School, London SE1 7EH, Great Britain
R. P. R. DAWBER, The Department of Dermatology, The Slade Hospital,
Headington, Oxford OX37JH, Great Britain
D. C. DUMONDE, Department of Immunology, St. Thomas's Hospital, Lambeth
Palace Road, London SE1 7EH, Great Britain
C. J. DUNN, Department of Hypersensitivity Diseases Research, The Upjohn
Company, Kalamazoo, MI 49001, USA
VI List of Contributors
J. A. EDWARDSON, Medical Research Council, Neuroendocrinology Unit, New
castle General Hospital, Westgate Road, Newcastle upon Tyne NE46BE,
Great Britain
V. EISEN, Department of Pharmacology and Therapeutics, Cobbold Laboratories,
Thorn Institute of Clinical Sciences, The Middlesex Hospital Medical School,
London W1N 8AA, Great Britain
B. A. ELLIS, Department of Immunology, St. Thomas's Hospital, Lambeth
Palace Road, London SE1 7EH, Great Britain
J. C. FOREMAN, The Department of Pharmacology, University College London,
Gower Street, London WC1E 6BT, Great Britain
M. J. FORREST, Merck Sharp & Dohme Research Laboratories, P.O. Box 2000,
Rahway, NJ 07065, USA
M. Goos, Medizinische Einrichtungen der UniversiHit, Hautklinik, Hufeland
str. 55, D-4300 Essen 1
M. W. GREAVES, Institute of Dermatology, St. Thomas's Hospital, Lambeth
Palace Road, London SE1 7EH, Great Britain
S. T. HOLGATE, Medicine I, Southampton General Hospital, Tremona Road,
Southampton S094XY, Great Britain
v. K. Hopsu-HAVU, Department of Dermatology, University of Turku,
SF-20520 Turku 52
A. B. KAY, Department of Allergy and Clinical Immunology, Cardiothoracic
Institute, Dovehouse Street, London SW3 6L Y, Great Britain
C. M. LAPIERE, Universite de Liege, Clinique Dermatologique, CHU de Baviere,
BId. de la Constitution, 66, B-4020 Liege
F. LAWLOR, Institute of Dermatology, St. Thomas's Hospital, Lambeth Palace
Road, London SE1 7EH, Great Britain
B. LYNN, Department of Physiology, University College London, Gower Street,
London WC1E 6BT, Great Britain
P. MAUVAIS-JARVIS, Reproductive Endocrinology Department, Hopital Necker,
149, rue de Sevres, F-75730 Paris Cedex 15
J. MORLEY, Preclinical Pharmacology, Sandoz Ltd., CH-4002 Basle
B. V. NUSGENS, Universite de Liege, Clinique Dermatologique, Hopital
de Baviere, BId. de la Constitution, 66, B-4020 Liege
E. M. SAIHAN, Department of Dermatology, University Hospital, Queen's
Medical Centre, Nottingham NG72UH, Great Britain
C. SCHUBERT, Department of Dermatology, Hautklinik, Christian-Albrechts
Universitiit, Schittenhelmstr.7, D-2300 Kiel
List of Contributors VII
S. SHUSTER, The University of Newcastle upon Tyne, Department of Dermatology,
The Royal Victoria Infirmary, Newcastle upon Tyne NEl 4LP, Great Britain
A. J. THODY, Department of Dermatology, The University of Newcastle upon
Tyne, The Royal Victoria Infirmary, Newcastle upon Tyne NEl 4LP, Great
Britain
G. VOLDEN, Department of Dermatology, Regional Hospital, University of
Trondheim, N-7006 Trondheim
A. J. WARDLAW, Department of Allergy and Clinical Immunology, Cardio
thoracic Institute, Brompton Hospital, Fulham Road, London SW36HP,
Great Britain
S. I. WASSERMAN, Division of Allergy/Rheumatology, Department of Medicine,
School of Medicine, University of California Medical Center, 225 Dickinson
Street, San Diego, CA 92103-9981, USA
T. J. WILLIAMS, Department of Applied Pharmacology, Cardiothoracic Institute,
Fulham Road, Brompton, London SW36HP, Great Britain
D. A. WILLOUGHBY, Department of Experimental Pathology, St. Bartholomews
Hospital Medical College, (University of London), West Smithfield, London
EC1A 7BE, Great Britain
F. WRIGHT, Faculte de Medecine, Pitie Salpetriere, Service de Biochimie Medicale,
91 Bid. Hopital, F-75634 Paris Cedex 13
M. A. ZAR, Department of Pharmacological Sciences, Medical School, University
of Newcastle upon Tyne, Newcastle upon Tyne NEl 4HH, Great Britain
V. A. ZIBOH, Department of Dermatology, TB 192-School of Medicine, University
of California Davis, Davis, CA 95616, USA
Preface
The recent interest in the pharmacology of the skin and the treatment of its
diseases has come about for two reasons. The first is a realisation that many
aspects of pharmacology can be studied as easily in human skin, where they
may be more relevant to human physiology and diseases, as in animal models.
Examples of this are the action of various vasoactive agents and the isolation of
mediators of inflammation after UV irradiation and antigen-induced dermatitis.
The second reason is the fortuitous realisation that a pharmacological approach
to the treatment of skin disease need not always await the full elucidation of
etiology and mechanism. For example, whilst the argument continued unresolved
as to whether the pilo-sebaceous infection which constitutes acne was due to a
blocked duct or to a simple increase in sebum production, 13-cis-retinoic acid
was found quite by chance totally to ablate the disease; again, whilst cyclosporin,
fresh from its triumphs in organ transplantation, has been found able to suppress
the rash of psoriasis, it has resuscitated the debate on etiology.
We are therefore entering a new era in which the pharmacology and clinical
pharmacology of skin are being studied as a fascinating new way of exploring
questions of human physiology and pharmacology as well as an important step
in the development and study of new drugs, use of which will improve disease
control and at the same time help to define pathological mechanisms.
It was because of this burgeoning interest in pharmacology of skin and its
diseases that this book came about. Indeed, it is long overdue and was planned
several years ago; we console ourselves with the thought that the delay may have
served to help define certain principles which were then only just emerging.
The book is divided into two volumes, which are independent but com
plementary, the first being an account of the general pharmacology of skin, and
the second being more concerned with disease and drugs. The first volume is
divided into two parts, the one dealing with the pharmacology of skin systems
and their control and the other with autocoids in normal and inflamed skin.
The second volume has three parts: the first part deals with the methods of
measurement which are becoming of increasing importance in studying both
the pharmacology and clinical pharmacology of skin; the second deals with
toxicology in its widest sense - including metabolism and percutaneous absorp
tion; and the third is an account of both specific drugs and the drugs used for
specific diseases.
The aim has been to give an up-to-date review in which there was sufficient
background detail for an understanding of the subject without having to refer
beyond the two volumes - but, of course, with sufficient referencing to serve as
x
Preface
a guide to deeper reading. Authors were encouraged to present both consensus
and personal views so that both possibilities and what appear today to be
probabilities are presented. In this way it is hoped that the two extremes of dogma
and fantasy have been avoided. In presenting this account we were well aware
of the problems of a rapidly advancing field, but we hope that the chapters are
so written that newer knowledge, which is now almost continuously becoming
available, can be more easily understood and incorporated into a body of
knowledge. Finally but inevitably, we have had to make certain omissions - for
example in the field of anti-viral drugs, AIDS and one or two other areas - if only
for reasons of size.
The volumes are written for pharmacologists, clinical and non-clinical, and
will be pertinent to pharmacists and to many with an interest in the skin now
working in the pharmaceutical industry, as well as to physiologists. The work
too will be of major interest to dermatologists. Although the book is directed
primarily at a postgraduate audience, there is much in it that will be of helpful to
Honours and Ph.D. students. We hope that by including as much background
as is relevant to an understanding within the two volumes, we will have
reduced the likelihood of the reader having to look elsewhere for primary
explanations'. This plan may have led to some duplication and over-simplifica
tion, but we hope readers will agree that this was justified by the overriding
objective. Finally we would like to thank our secretaries, Miss ANGELA DELL and
Mrs. MADELINE YOUNG, for their inexplicably angelic assistance.
MALCOLM W. GREAVES
SAM SHUSTER
Contents
Section A: Pharmacology of Skin Systems
CHAPTER 1
The Epidermis
E. CHRISTOPHERS, C. SCHUBERT, and M. Goos. With 9 Figures 3
A. The Structure of Epidermis. . . 3
I. The External Surface of Skin 3
II. Histology of Epidermis 5
1. Introduction. . . . . . 5
2. The Basement Membrane 6
3. Fine Structure of Epidermal Cells. 8
4. Lamellar Granules . . . . . . . 10
5. Intercellular Junctions. . . . . . 11
6. Regional Differences in Epidermal Structure 13
B. Epidermal Replacement . . . . . 14
I. Epidermal Renewal Rates . . . . 14
II. Effects of External Influences. . . 15
III. Migration Out of the Basal Layer. 16
IV. The Formation of Epidermal Cell Columns. 17
V. The "Zipper Mechanism" Leading to Column Formation 19
C. The Langerhans Cell 21
I. Morphological Features 21
II. Origin. . . . . . . 24
III. Functional Properties 24
IV. Role in Disease. 24
D. Conclusion. 25
References. . . . . . . 25
CHAPTER 2
Keratin
H. P. BADEN. With 7 Figures 31
A. Introduction . . 31
B. Fibrous Proteins 32
C. Keratohyalin. . 36
XII Contents
D. Cornified Envelope . . . . . 38
E. Desmosomes . . . . . . . . 40
F. Membrane Coating Granules. 41
References. . . . . . . . . . . 41
CHAPTER 3
Regulation of Epidermal Growth
E. M. SAlHAN . . . . . . . . . . . . . . . . . . . . . 45
A. Cyclic Nucleotides . . . . . . . . . . . . . . . . . 45
I. Effects of Cyclic AMP on Different Epidermal Cells . 45
II. Cyclic GMP 47
III. Receptors . . . . . 47
B. Prostaglandins . . . . . 48
C. Epidermal Growth Factor 49
I. Chemical Composition and Properties 49
II. Human EGF . 50
III. Level of EG F . . . . . . . . . . 50
IV. EGF Receptor . . . . . . . . . . 50
V. EGF in Cell Proliferation and Differentiation. 51
D. Chalones of the Skin . . 51
E. Calcium and Calmodulin. 52
F. Histamine . 53
G. Conclusion. 53
References. . . 54
CHAPTER 4
Epidermal Lipogenesis (Essential Fatty Acids and Lipid Inhibitors)
V. A. ZIBOH. With 3 Figures . . . . . . . . . 59
A. Introduction and Historical Considerations . 59
B. Essential Fatty Acids . . . . . . . . 60
I. Biosynthesis and Metabolism. . . . . 60
II. Physiological Functions in the Skin . . 60
III. Role as Precursors of Prostaglandins and Related Lipids 61
C. Essential Fatty Acid Deficiency. . . . . . . . . . . . . 61
I. Macroscopic and Microscopic Appearance of the Skin During
Deficiency . . . . . . . . . . . . . . . . . 61
II. Altered Patterns of Polyunsaturated Fatty Acids 62
III. Increased Metabolic Activity During Deficiency . 63
IV. Deficiency in Human Skin . . . . . . . 63
D. Epidermal Lipogenesis and Its Regulation . . 64
I. Interrelationships of Metabolic Pathways. 64
II. Regulation of Epidermal Lipogenesis 65
References. . . . . . . . . . . . . . . . . . 66