Table Of ContentHANS SELYE SYMPOSIA ON
NEUROENDOCRINOLOGY AND STRESS
Series Editors:
Sandor Szabo, Harvard Medical School, Boston, Massachusetts
Yvette Tache, UCLA, Los Angeles, California
Beatriz Tuchweber-Farbstein, University of Montreal, Montreal Quebec, Canada
Volumes published by Plenum Press:
Volume 2—NEUROENDOCRINOLOGY OF GASTROINTESTINAL
ULCERATION
Edited by Sandor Szabo and Yvette Tache
Volume 3—ADVANCES IN PSYCHONEUROIMMUNOLOGY
Edited by Istvan Berczi and Judith Szelenyi
NEUROENDOCRINOLOGY
OF GASTROINTESTINAL
ULCERATION
Edited by
Sandor Szabo
Harvard Medical School
Boston, Massachusetts
and University of California, Irvine
VA Medical Center
Long Beach, California
and
Yvette Tache
Center for Ulcer Research and Education
University of California, Los Angeles
Los Angeles, California
Associate Editor
Gary B. Glavin
University of Manitoba
Winnipeg, Manitoba, Canada
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
NEUROENDOCRINOLOGY
OF GASTROINTESTINAL
ULCERATION
Library of Congress Cataloging-1n-Publ1catIon Data
Neuroendocrmo logy of gastrointestinal ulceration / edited by Sandor
Szabo and Yvette Tache associate editor, Gary B. Glavin.
;
p. cm. — (Hans selye symposia on neuroendocrtno 1 ogy and
stress v. 2)
;
Includes bibliographical references and index.
ISBN 978-1-4613-5759-9 ISBN 978-1-4615-1867-9 (eBook)
DOI 10.1007/978-1-4615-1867-9
1. Peptic ulcer—Pathophysiology. 2. Neuroendocr1 no 1ogy.
I. Szabo, Sandor, 1944- . II. Tache, Yvette. III. Glavin, Gary
B. IV. Series.
[DMLM: 1. Peptic -Ulcer—physlopathology. 2. Gastric Mucosa-
-secretlon, 3. Stress—phys1opatho1ogy. 4. Disease Models, Animal.
WI 350 N495 19953
RC821.N44 1995
616.3'4307—dc20
DNLM/DLC
for Library of Congress 95-14350
CIP
Proceedings of a meeting on Neuroendocrinology of Gastrointestinal Ulceration,
held September 13-15, 1989, in Esterel, Quebec, Canada
ISBN 978-1-4613-5759-9
© 1995 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1995
Softcover reprint of the hardcover 1 st edition 1995
109 8 7 6 5 4 3 2 1
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
IN MEMORIAM: MARC CANTIN, PRESIDENT HANS SELYE FOUNDATION
1933·1990
Dr. Cantin died on June 17, 1990 in Montreal at the age of 57. A native of
Quebec City, he completed his studies up to Doctor of Medicine (1958) from the
University of Laval. Following this training, he went to the University of Montreal
and received a Ph.D. in Experimental Medicine and Surgery under the leadership of
Dr. Hans Selye. Subsequently, he specialized in anatomical pathology at the
University of Chicago in the Department of Anatomical and Experimental Pathology.
Since 1984, Dr. Cantin was Director of the Multidisciplinary Research Group on
Hypertension at the Institute of Clinical Research of Montreal and Professor of
Pathology at the University of Montreal. He directed a very productive group and
authored 379 papers. He will be remembered for his important scientific
contributions which addressed the role of the endocrine system in the pathogenesis
of cardiovascular diseases.
Dr. Cantin was a recipient of several awards, including the Marcel Piche prize
and the Leo Parizeau prize. In 1988 he received, together with Dr. P. Needelman,
the Research Achievement Award from the American Heart Association for their
work on the atrial natriuretic factor. Dr. Cantin was a member of the editorial boards
of several scientific journals, president of the Medical Advisory Board of the Cancer
Research Society and had been the first president of the Hans Selye Foundation, a
post he held since 1982. He spent his life totally devoted to his work and scientific
responsibilities. Each meeting with him revealed his commitment, enthusiasm and
grcat internal resources for reaching goals. We will miss him as a friend and
colleague. This book will be an appropriate tribute to his memory since he played
an important role in the organization of this symposium in Esterel, Quebec, Canada.
Yvette Tache, Ph.D.
Sandor Szabo, M.D., Ph.D.
Vice Presidents, Hans Selye Foundation
v
PREFACE
Selye pioneered the concept of biologic stress and contributed to the exploration
of this field for over 40 years. He established the Hans Selye Foundation in 1980 to
promote research and education on stress. In the spirit of the Foundation, Dr. Marc
Cantin, late president, and Drs. Sandor Szabo and Yvette Tache, vice presidents, have
established the Hans Selye Symposia on Neuroendocrinology stress conference and
book series. So far three symposia have been held in Montreal where Selye started
to work in the 1930's. These symposia bring together laboratory and clinical
investigators engaged in the study of the neuroendocrinology, pathophysiology of
stress, and related fields.
The first Hans Selye Symposium, held in 1986, was devoted to "Neuropeptides
and Stress" and the proceedings were published by Springer Verlag. In 1992, in
commemoration of the tenth anniversary of Selye's passing in October 1982, another
Hans Selye Symposium was organized and was entitled "Corticotropin-Releasing
Factor and Cytokines: Role in the Stress Response". The proceedings recently
appeared in 1993 as volume 697 of the New York Academy of Sciences.
A substantial part of the present volume originates from the Hans Selye
Symposium and devoted to the "Neuroendocrinology of Gastrointestinal Ulceration".
A section on the novel therapeutic methods of approach to gastrointestinal ulceration
encompasses the influence of calcium modulators, dopaminergic agents, dietary
factors and growth factors in the development of experimental ulcers. Several
chapters deal with the complex problems of the underlying neural mechanisms
involved in the pathogenesis and prevention of gastrointestinal ulceration. In
particular, emphasis has been placed on the role of the vagus and the sympatho
adrenergic regulation of defensive mechanisms such as bicarbonate secretion and
sensory nerves. Advances in the understanding of the chemical coding and
neuroanatomical substrata of the brain which influence gastric function and ulcer
formation are summarized in the last portion of the book. More specifically covered
are the role of medullary thyrotropin-releasing hormone in the vagal dependent
formation of gastric lesions and of brain corticotropin-releasing factor in stress-related
alterations of gastrointestinal function. Mounting evidence of the key influence of the
limbic and mesolimbic system in stress ulcer formation is also presented.
The editors are exceedingly grateful to all the contributors who have enabled us
to produce a comprehensive survey of knowledge in the field of the
neuroendocrinology of gastrointestinal ulceration. With respect to the preparation
of this volume, we would like to express our thanks to Mrs. Carroll Powney for her
meticulous typing and proofreading of the manuscript.
Sandor Szabo
Yvette Tache
Gary Glavin
vii
ACKNOWLEDGMENTS
We would like to express our deep appreciation to the patrons and sponsors of the "Hans
Selye Symposia on Neuroendocrinology and Stress: Neuroendocrinology of Gastrointestinal
Ulceration" for their support of the excellent international conference:
Patrons of the Symposium
Hans Selye Foundation
Medical Research Council of Canada
Angio-Medical Corporation
Kali -Chernie-Pharrna
Marion Laboratories
Sponsors of the Symposium
Ayerst Laboratories
Fond de la recherche en sante du Quebec
Kotobuki Seiyaku Co., Ltd.
Nordic Laboratories, Inc.
Rorer Group, Inc.
G.D. Searle and Co.
UCLA Brain Research Institute
Universite de Montreal
The Upjohn Co.
Personally, we would like to thank the late Dr. Marc Cantin, fonner President of the
Hans Selye Foundation, Mrs. Louise Drevet-Selye, Dr. Pierre Bois, fonner President of
the Medical Research Council of Canada, Dr. Arnold Scheibel, Director of the Brain
Research Institute, UCLA, Los Angeles, as well as Joyce Fried, Assistant Dean for
Educational Administration, UCLA School of Medicine, who dedicated her excellent
organizational skills to coordinate all aspects of the conference. We are also grateful to
Mrs. Carroll Powney for excellent manuscript preparation for this volume.
Finally, we thank the conference participants and authors of the chapters in this
volume, who prepared and revised manuscripts and whose contributions represent an up
to-date survey of the neuroendocrinology of gastrointestinal ulceration.
Sandor Szabo, Boston
Yvette Tache, Los Angeles
Gary Glavin, Winnipeg
ix
CONTENTS
NEUROENDOCRINE FACTORS IN ULCER PATHOGENESIS
Role of Sensory Neurons in the Control of Gastric Mucosal Blood Flow and
Protection ..................................................... .
Peter Holzer, Irmgard Lippe, Milana Jocic, Ch. Wachter, Rainer Amann,
M. Pabst, A. Heinemann, Birgitta M. Peskar, Helen Raybould,
Edward Livingston, Helen Wong, John Walsh, Yvette Tache, and Paul Guth
Syrnpatho-Adrenergic Regulation of Duodenal Mucosal Alkaline Secretion. . . . . . . .. 15
Lars Fiindriks, and Claes Jonson
Potentiation of Intestinal Secretory Responses to Histamine: Pathophysiological
Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 25
Patangi Rangachari, Todd Prior, and Russell Bell
Acidosis Plays an Important Role in Stress-Induced Gastric Ulceration in Rats ...... 33
Chi-Hin Cho, Marcel Koo, and Clive Ogle
The Development of Acute Gastric Mucosal Lesions Following Bum Stress ........ 43
Masaki Kitajima, Masashi Yoshida, Yoshihide Otani, and Kouichiro Kumai
Experimentally Induced Duodenal Ulcers in Rats Are Associated with a Reduction
of Gastric and Duodenal Calcitonin Gene-Related Peptide-Like
Immunoreactivity ............................................... 53
Stefano Evangelista, Paola Mantellini, and Daniela Renzi
The Effect ofbFGF and PDGF on Acute Gastric Mucosal Lesions, Chronic Gastritis
and Chronic Duodenal Ulcer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 61
Sandor Szabo, Judah Folkman, Stefano Kusstatscher, Zsuzsa Sandor, and
Michael M. Wolfe
Animal Models and Pathogenesis of Inflammatory Bowel Disease ................ 73
Gerald Morris, Paul Beck, John Wallace, Margaret Herridge, and
Carlo Fal10ne
Leukotrienes in Human and Experimental Ulcerative Colitis. . . . . . . . . . . . . . . . . . . .. 93
John Wallace, Gerald Morris, and Catherine Keenan
The Brain-Gut Axis and the Mucosal Immunoinflammatory Response ............. 103
Fergus Shanahan
xi
BRAIN-GUT INTERACTIONS IN ULCER PATHOGENESIS
Neuroendocrine Control of Gastric Acid Secretion ............................. 109
Yoshitsugo Osumi, Yasunobu Okuma, Kunihiko Yokotani, Mitsuhiro Nagata,
and Toshio Ishikawa
Role of Corticotropin-Releasing Factor in Stress-Induced Changes in
Gastrointestinal
Transit ........................................................ 119
Thomas Burks
Stress, Corticotrophin-Releasing Factor (CRF) and Gastric Function .............. 123
Herbert Weiner
Corticotropin Releasing Factor and Gastric Erosions ........................... 133
Hans-Kristian Bakke, and Robert Murison
The Limbic System and Stress Ulcers ....................................... 139
Peter Henke
Neurotensin Acts in the Mesolimbic Dopamine System to Affect Gastric Mucosal
Function ....................................................... 151
Gordon Kauffman, Lianping Xing, and Robert Bryan
Role of Medullary Trh in Vagally Mediated Formation of Gastric Lesions .......... 161
Yvette Tache, Hond Yang, Masashi Yoneda, and Bruno Bonaz
Role of the Vagal Nerve in the Development of Gastric Mucosal Injury and Its
Prevention by Atropine, Cimetidinc, p-Carotcnc and Prostacyclin in Rats .. 175
Gyula Mozsik, Beata Bodis, Maria Garamszegi, Oszkar Kanidi,
Agnes Kiraly, Lajos Nagy, Gabor Suto, Gyula Toth, and Aron Vincze
The Role of Vagal Innervation in Adaptive Cytoprotection ....................... 191
Thomas Miller, Gregory Smith, Michael Tomwall, Rafael Lopez,
Julia Henagan, and Karmen Schmidt
A Biobehavioral Profile of an Ulcer Susceptible Rat Strain ...................... 20 I
William Pore and Eva Redei
NOVEL THERAPEUTIC APPROACHES TO GASTROINTESTINAL ULCERATION
The Gastric Mucosal Barrier: a Dynamic, Multifunctional System ................ 209
Andrew Garner, Paul Rowe, and Jeffrey Matthews
New Approaches to Gastroprotection: Calcium Modulators ...................... 215
Gary B. Glavin and Arleen M. Hall
Efficacy of Dopaminergic Agents in Peptic Ulcer Healing and Relapse Prevention:
Further Indication of the Importance of Stomach Dopamine in the
Stress-Organoprotection Concept ................................... 221
Predrag Sikiric, Iva Rotkvic, Stjepan Mise, Sven Seiwerth,
Zeljko Grabarevic, Marijan Petek, Rudolf Rucman, Vanja Zjacic-Rotkvic,
Marko Duvnjak, Vjekoslav Jagic, Ernest Suchanek, Anton Marovic,
Marko Banic, Tomislav Brkic, Miro Hanzevacki, ladranka Separovic,
Sanja Djacic, and Velimir Simicevic
xii
Dietary Factors Influencing Gastrointestinal Ulceration: the Luminal Regulatory
System ........................................................ 231
Francisco Guamer, Jaime Vilaseca, Antonio Salas, Rosa Rodriguez, and
Juan-R. Malagelada
Contributors ............................................................ 239
Index ................................................................. 247
xiii
