Table Of ContentMechanisms of
Gastroi ntesti nal
Motility and Secretion
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Volume SO-Mechanisms of Gastrointestinal Motility and Secretion
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Series A: Life Sciences
Mechanisms of
Gastrointestinal
Motility and Secretion
Edited by
Alan Bennett
King's College
School of Medicine and Dentistry
and
Giampaolo Velo
University of Verona
Verona, Italy
Plenum Press
New York and London
Published in cooperation with NATO Scientific Affairs Division
Proceedings of a NATO Advanced Study Institute on
Mechanisms of Gastrointestinal Motility and Secretion,
held September 5-16, 1983,
in Erice, Sicily, Italy
Library of Congress Cataloging in Publication Data
NATO Advanced Study Institute on Mechanisms of Gastrointestinal Motil
ity and Secretion (1983: Erice, Sicily)
Mechanisms of gastrointestinal motility and secretion.
(NATO ASI series. Series A, Life sciences; v. 80)
"Proceedings of a NATO Advanced Study Institute on Mechanisms of
Gastrointestinal Motility and Secretion, held September 5-16, 1983, in
Erice, Sicily, Italy"-Verso t.p.
"Published in cooperation with NATO Scientific Aftairs Division."
Includes bibliographical references and index.
1. Gastrointestinal system-Motility-Congresses.
I. Bennett, Alan, 1936- 11. Velo, G. P. 111. North Atlantic Treaty
Organization. Scientific Aftairs Division. IV. Title. V. Series.
QP180.N38 1983 612'.32 84-16045
ISBN 978-1-4684-4855-9 ISBN 978-1-4684-4853-5 (eBook)
DOI10.1007/978-1-4684-4853-5
©1984 Plenum Press, New York
Softcover reprint of the hardcover 1s t edition 1984
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233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
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P~FOCE
Gastroenterology is a large and diverse topic, and because of
this scientists working in one area often know little of advances
in other areas. This is particularly undesirable in a system with
different functions that interact and affect each other. But to
discuss the many aspects and their interactions adequately requires
more time than is generally available at meetings. A lO-day Inter
national School of Pharmacology on "Mechanisms of Gastrointestinal
Motility and Secretion" was therefore organised in Erice, Sicily,
September 1983, kindly supported by NATO. This book combines the
chapters written by the internationally recognised authorities who
participated, and reflects the breadth and the depth of the sub
ject matter.
Alan Bennett
Giampaolo Velo
v
CONTENTS
Anatomy of the gastrointestinal tract in relation to
motilit y and secretion •. • • • • • . • • • • • • • • • . • • • • . • • • • . • • • . . • • 1
Jeremy R. Jass
Techniques for studying gastrointestinal motility in
vitro • • • • • . • . • . • . • . . • • . . • • • • • • • • • . . • . . . • . • . . • . • • . . • • .. .• 13
Gareth J. Sanger and Alan Bennett
Motility: Methods for in vivo measurements • • • • • • • • • • • • • • • • •• 35
Paul Bass and Deborah A. Fox
Smooth muscle electrophysiology • • • • • • • • • • • • • • • • • • • • • • . • • • • • •• 55
Joseph H. Szurszewski
Electrophysiological studies of myenteric neurons in
tissue culture • . . . • • • • . • . • • . . • . • • . . • . • • . . . • . . • • • • . • • . . •. 73
Menachem Hanani
Gastrointestinal nerves, hormones and autacoids in
relation to human gastrointestinal motility ••.•••••••••. 87
Alan Bennett
Distribution of gut peptides and their actions ..•......•..•.. 109
Susan M. Wood
Histamine and the digestive functions ••..•.•.•••••••.•.•••.•• 117
Giulio Bertaccini and Gabriella Coruzzi
Relationships of prostaglandins to gastrointestinal
motility and secretion ••••.•••.•••.••••••..•..•••...•..• 129
Alan Bennett and Gareth J. Sanger
Gallbladder motility and its regulation •.•••••.••••••••.••••.. 159
John R. Wood and David R. Jenkins
Histopathological findings relating to disordered
motility and secretion ••.•.••••••..•.••••••••.••....••.• 177
Jeremy R. Jass
vii
Neuro-hormonal control of gastric acid secretion:
The role of histamine .••••••.••••••••••.•••.••••..•.••••• 189
Stanislaw J. Konturek
Gastrointestinal mucus .•••.••.•.•.•..••••.••.••.•••••.•••.•.• 205
A. Allen, N. Carroll, A. Garner, D.A. Hutton
and C.W. Venables
Intestinal absorption and secretion of fluid and
electrolytes .•••....••••••••..••••.•••.••••••••.••••...•. 219
Henry J. Binder
Gallbladder fluid transport .•..•..••..•••.•..•...••.••...•••• 229
John R. Wood and Joar Svanvik
Relationships among intestinal motility, transit
and absorption •••••.•••..•.•...•••...•.•.•••...••...••..• 239
Sidney F. Phillips
The entero-insular axis •..••••..•..•.........•••..•.....•..•• 259
Susan M. Wood
Neuro-hormonal control of exocrine pancreatic
secretion in humans and animals .••••.•...•.•..•.••....... 277
Manfred V. Singer
Acute and chronic actions of alcohol on pancreatic
exocrine secretion in humans and animals .................. 281
Manfred V. Singer
Dopamine antagonists as anti-emetics and as
stimulants of gastric motility ......... , .................. 287
Brian McRitchie, Christine M. McClelland
Stephen M. Cooper, David H. Turner and
Gareth J. Sanger
Mechanisms by which metoclopramide can increase
gastrointestinal motility ......................•.......... 303
Gareth J. Sanger
Laxatives: A review of their mechanisms of action ............ 325
Paul Bass and Deborah A. Fox
Lectures ......................................................
345
..................................................
Participants
347
.........................................................
Index
349
viii
ANATOMY OF THE GASTROINTESTINAL TRACT IN RELATION TO
MOTILITY AND SECRETION
Jeremy R. Jass
Department of Histopathology
Westminster Medical School
London SW1P 2AR UK.
INTRODUCTION
A broad outline of the structure of the gut will be
given, slanted towards the activities of motility and
secretion. Emphasis will be placed on the functional
divergence of epithelial secretory cell populations.
BASIC STRUCTURE OF GUT
The wall of the alimentary canal shows a similar
structure throughout its length. Four layers are
constantly present including the serosa, muscularis
externa, submucosa and mucosa. The serosa (peritoneum)
comprises a mesothelium and a connective tissue layer.
The muscularis externa is arranged in an inner circular
and an outer longitudinal layer of smooth muscle. Located
between them is the myenteric (Auerbach's) plexus. In the
stomach three somewhat indistinct muscle layers have been
detailed. Striated muscle forms the upper third of the
oesophageal muscularis externa. The submucosa is composed
of loosely arranged connective tissue, which allows the
mucosa to adopt its characteristic pattern of folds.
Within it is the submucous (Meissner's) plexus, which is
less conspicuous than the myenteric plexus. It is
particularly poorly developed in the oesophagus. Sub
mucosal glands are found in the oesophagus and duodenum
(Brunner's). Conspicuous lymphoid aggregates (Peyer's
patches) occur in the terminal ileum.
The mucosa includes the muscularis mucosae, lamina
propria and lining epithelium. The lamina propria is
composed of delicate connective tissue and within it
are found fibroblasts, mast cells, macrophages, lympho
cytes, plasma cells and eosinophils. The mucosal lining
of the oesophagus and anal canal is a non-keratinised
stratified squamous epithelium. The remainder of the gut
is lined by a columnar epithelium. This varies according
to the different regions and will be discussed in more
detail below.
INNERVATION OF THE GUT
The nerve supply to the gut may be divided into
extrinsic and intrinsic components. The extrinsic
innervation of the gut is through the autonomic nervous
system, which is divided into sympathetic and para
sympathetic components. The parasympathetic supply to the
oesophagus, stomach, small intestine and proximal colon
is through the vagus nerve. The colon is also innervated
through the sacral spinal nerves. The preganglionic fibres
terminate in the myenteric plexus. An exception are the
fibres supplying the striated muscle of the oesophagus
which terminate as motor end plates. The vagus contains
many afferent fibres to complete possible reflex loops.
The sympathetic supply is through lower thoracic and
lumbar spinal nerves. These end in prevertebral ganglia
(coeliac, superior mesenteric, inferior mesenteric) which
are closer to the spinal cord than the organs to be
innervated. The postganglionic fibres terminate in either
the myenteric or submucous plexus, or may supply sphinct
eric smooth muscle directly. The sympathetic nerves also
contain afferent fibres whose cell bodies may reside
either within the gut (eg. acting as mechanoreceptors) or
within the dorsal root ganglia. These will complete short
and long reflex circuits respectively. The intrinsic
innervation is through the myenteric and submucosal
plexuses. These are composed of intercommunicating ganglia
in which are found nerve (ganglion) cell bodies, nerve
processes and glia. Most of the direct innervation of
smooth muscle is through the intrinsic neurons of the two
plexuses (Baumgarten, 1982).
The intrinsic neurons which act directly on the
smooth muscle of the gut wall are of two types. These are
excitatory, mainly cholinergic neurons and inhibitory
non-cholinergic neurons. The former are driven either
by excitatory interneurons or extrinsic preganglionic
cholinergic fibres. They are inhibited either directly
by extrinsic postganglionic adrenergic fibres or in-
2
directly through presynaptic inhibition of excitatory
interneurons. The inhibitory, non-cholinergic fibres
supplying smooth muscle are again driven either by
excitatory interneurons or extrinsic, preganglionic
cholinergic (parasympathetic) fibres. Some interneurons
may also be inhibitory. It is clear that noradrenaline·
and acetyl choline are not the only neurotransmitters
released within the gut and a variety of alternatives
have been proposed for the non-adrenergic, non-cholinergic
neurons (Furness and Costa, 1982). 5 hydroxytryptamine
is a likely candidate (Gershon and Erde, 1981) though no
specific role for 5HT nerves has been identified. Vaso
active intestinal polypeptide may act as the neurotrans
mitter for the inhibitory neurons supplying smooth
muscle whereas substance P may function as an excitatory
neurotransmitter (Furness and Costa, 1982).
Before the advent of immunohistochemistry, the
neurons of the myenteric plexus were classified accord
ing to whether or not they were argyrophil and cholin
esterase positive (Smith, 1970). Unfortunately these
classical light microscopic techniques show no clear
correlation with current functional classifications in
which the neurotransmitter substances are identified
histochemically and ultrastructurally (Burnstock,1981).
SMOOTH MUSCLE
The smooth muscle cells of the gut are spindle
shaped and covered by a thin basement membrane. At the
cell surface are caveolae or pinocytotic invaginations
which may be associated with the smooth endoplasmic
reticulum. These are possibly involved in Ca 2+ transport.
Three types of cytoplasmic filament have been identified -
thin (actin), intermediate (desmin) and thick (myosin).
Dense bands are also present, but without the regular
organization of striated muscle. Electrical coupling is
achieved through the junctional complexes which are of
three types - interdigitations, gap junctions (nexuses)
and intermediate junctions (Gabella,1979). The electron
dense material on the cytoplasmic side of the intermediate
junction is anchored by intermediate filaments. Individual
muscle cells are not necessarily supplied by nerve
terminals. Nerve processes with bead-like varicosities
surround groups of muscle fibres and neurotransmitters
are released into tissue spaces to reach the target cells
by diffusion.
3
