Table Of ContentAutonomic and Enteric
Ganglia
Transmission and Its Pharmacology
Autonomic and Enteric
Ganglia
Transmission and Its Pharmacology
Edited by
Alexander G. Karczmar
Loyola University Stritch School of Medicine
Maywood. Illinois
Kyozo Koketsu
and
Syogoro Nishi
Kurume University School of Medicine
Kurume. Japan
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Autonomic and enteric ganglia.
Includes bibliographies and index.
1. Ganglia, Autonomic. 2. Neural transmission. 3. Ganglionic blocking agents. 4.
Ganglionic stimulating agents ..I . Karczmar, A. G. (Alexander George), 1918- . II. Koket
su, Kyozo, 1922- . III. Nishi, Syogoro. [DNLM: 1. Ganglia, Autonomic-physiology. 2.
Ganglionic Blockaders-pharmacodynamics. 3. Gastrointestinal System-innervation. 4.
Neural Transmission. 5. Neuroregulators-pharmacodynamics. WL 600 A9388j
QP368.8.A96 1985 612'.89 85-19398
ISBN-13: 978-1-4615-9438-3
© 1986 Plenum Press. New York
Soft cover reprint of the hardcover I st edition 1973
A Division of Plenum Publishing Corporation
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
in any form or by any means, electronic, mechanical, photocopying, microfilming,
ISBN-13: 978-1-4615-9438-3 e-ISBN-13: 978-1-4615-9436-9
DOl: 10 .1 0071 978-1-4615-9436-9
Foreword
In the early 1960s, Dr. Alexander G. Karczmar, Professor of Pharmacology
and Experimental Therapeutics at the Stritch School of Medicine of the
Medical Center at Loyola University of Chicago, was confronted with a
certain technical problem concerning his studies of synaptic transmission
by means of microelectrode methods. He thought that the problem might
be resolved if he could interest a microelectrode expert such as Dr. Kyozo
Koketsu in his studies. Dr. Koketsu was a past member of the Faculty of
the Kurume University School of Medicine who as a Research Fellow at
the Australian National University had helped Sir John Eccles, subse
quently a Nobel Prize winner, in developing microelectrode procedures.
After further considering the matter, Dr. Karczmar was pleasantly sur
prised to discover that by coincidence Dr. Koketsu was his neighbor,
serving at that time as a Research Professor at the Neuropsychiatry Institute
of the University of Illinois, College of Medicine of Chicago. This was the
beginning of a long relationship, as Dr. Koketsu joined Dr. Karczmar at
Loyola as Professor of Pharmacology and Therapeutics and Director of the
Neurophysiology Laboratory at the Stritch School of Medicine. It was not
long before Dr. Syogoro Nishi-Dr. Koketsu's former colleague on the
Faculty of Medicine at Kurume University, and at that time a Research
Fellow in Neurophysiology at the Rockefeller Institute in New York
joined Drs. Koketsu and Karczmar at Loyola. Although in due time Drs.
Nishi and Koketsu returned to their alma mater (where Dr. Nishi is today
a Professor of Physiology and Dr. Koketsu is Dean and President of the
Kurume University School of Medicine), the friendship and teamwork of
these three men lasted beyond their time together at Loyola and continues
today.
Working together, Drs. Karczmar, Koketsu, and Nishi established at
the Stritch School of Medicine a nucleus of synaptic (including ganglionic)
researchers, and their laboratories became the center of activities for their
students, research associates, postdoctoral fellows, and visiting investi-
v
vi Foreword
gators. Among the members of their team were scientists from Europe
(including Poland, France, Russia, England, and Scotland), Australia, Ja
pan, and China. And the research in these truly international laboratories
led to many discoveries that helped clarify processes of synaptic trans
mission that constitute the basis of CNS function and behavior. After the
return of Drs. Koketsu and Nishi to Japan, the research and training ac
tivities of what then became a Loyola-Kurume group were continued, and
there was a continuous exchange of personnel between Kurume and Chicago.
This book is a result of these many years of friendship and teamwork,
as the editors of this book-which I trust is both unique and remark
able-and the authors are men and women who have worked together,
whether at Loyola or Kurume.
As the Provost of the Medical Center of Loyola University of Chicago,
I am pleased to recall this history of research and training development
involving both this Center and Kurume University Medical School. I am
happy that Loyola University Medical Center contributed to the support
of the investigations of Drs. Karczmar, Koketsu and Nishi, and of their
associates. Similarly, we were happy to provide all the help we could
during the planning session for this book and during its final preparation.
I know that this book constitutes only one stage in the research and
training activities of Kurume University School of Medicine-Loyola Uni
versity Medical Center, and that more papers and texts will result in the
future from this notable international cooperation.
Richard W. Matre, Ph.D.
Provost
Loyola University Medical Center
Maywood, Illinois
Preface
This book was planned by the editors with a specific aim and a defined
philosophy. The aim was to describe the transmission processes and re
lated phenomena in vertebrate autonomic and enteric ganglia; the phi
losophy was to present the pertinent information as a unified whole, with
as focused an approach as possible, avoiding any degree of tangentiality,
even at the risk of occasional incompleteness.
There was an additional aspect to this book: It was to be authored by
a team of friends of long standing who were in a good position to prepare
a cohesive, homogeneous text, since they had been co-workers for many
years in ganglionic research and had published many papers and reviews
together.
Once the book's philosophy and aims had been decided on by the
editors, its plan could be laid down almost automatically and its chapters
assigned as appropriate for the interests and research experience of the
members of the team. First of all, it appeared self-evident that to render
ganglionic transmission and its processes intelligible, an understanding
of the anatomy, electrophysiology, and neuropharmacology of autonomic
and enteric ganglia was needed. Accordingly, this book emphasizes the
anatomy, histology, and cytology as well as the cytochemistry of the sym
pathetic and parasympathetic ganglia and of the enteric neurons. With
this as the substrate for the dynamic events of autonomic ganglionic and
enteric transmission, the characteristics of the membranes involved in
this transmission are described. The responses, both pre- and postsyn
aptic, of the ganglionic and enteric membranes are described in detail, as
are the electrophysiological characteristics of these responses and their
ionic generation. The transmitters involved in the various responses and
their presynaptic or intraneuronal origin, the release mechanisms, and
the postsynaptic sites of their action are also discussed. Furthermore, the
molecular bases of these responses-the receptors and the channels-are
described. Thus, the concepts of ganglionic and/or enteric nicotinic, mus-
vii
viii
Preface
carinic, and peptidergic transmission are explored in terms of their gen
eration, electrophysiology, and types of responses. To this end, attention
is focused on bioactive substances, whether active as endogenous trans
mitters and modulators or as exogenous substances that affect the ganglia
pre- or postsynaptically when applied to the ganglia. Thus, this topic
merges with a consideration of the pharmacology of ganglionic transmis
sion. Furthermore-since it is clear that endogenous bioactive substances
as well as pharmacological agents ultimately affect the ganglia via certain
energy processes that they generate-the role of second messengers in the
generation of ganglionic potentials is considered. The numerous refer
ences in this text to the many substances known today as transmitters
and putative transmitters-such as histamine, catecholamines, serotonin,
GABA and other amino acids, bioactive peptides including substance P
and enkephalins, and, of course, acetylcholine as well as second messen
gers (cyclic nucleotides and the components of the phosphatidylinositol
cycle)-reflect the concept, first enunciated in the eighteenth century, that
ganglia constitutes "little brains." In fact, one chapter in this book con
cerns the ganglia as a convenient model for the study of the CNS.
Finally, it was necessary to include a discussion of the presynaptic
spinal neurons and reflexes, including the afferent cells, since the ganglia
and the enteric system are activated preganglionically at the afferent end
of the reflex. In this same context, it was important to cover physiological
aspects of transmission, particularly in organs endowed with as much
autonomic peripheral control as the neurons of the enteric system, in
cluding ascending and decending excitations and inhibitions.
On the other hand, to achieve the desired focus, the editors decided
that such subjects as embryonic development of the ganglia and the enteric
system, ganglionic metabolism, invertebrate ganglia, and the physiology
and pharmacology of effector organs did not belong in this book. Nor does
this book include descriptions of specific research topics.
Yet, within this entity, there is complexity, as behooves the "little
brains." The full significance of this complexity and of the "little brain"
concept gradually became apparent in the course of ganglionic and enteric
studies beginning during the nineteenth century. The historical devel
opment and emergence of this concept, presented in the first chapter of
this book, not only provide an exciting insight into the heuristic thinking
and experimental elegance of the work of our predecessors-such as Lang
ley and Dale; Feldberg, Kibjakow, and MacIntosh; and Eccles, Biilbring,
and Zamis-but also serve to clarify the components of this complexity.
In addition, Chapter 3 seeks to define and classify the various processes
and their interactions that bring about point-to-point control of ganglionic
and enteric transmission, and to provide a bird's-eye view of the current
status of concepts of ganglionic transmission and its multifactorial regulation.
Who may benefit from reading this book? Since mathematical, bio-
Preface ix
physical, and transmitter aspects of membrane function and ganglionic
potentials and their generation are described in some detail, synaptologists
and other neuroscientists should be included among its readers. Since the
ganglia clearly exemplify the processes of synaptic transmission and of
their modulation-processes that cannot be as easily analyzed in the CNS
neurologists should also profit from reading this volume. Furthermore,
since this book concerns the classic subject of autonomic and enteric
transmission, pharmacologists of any ilk should find some interest and
pleasure in perusing these chapters. By the same token, clinicians who
are concerned with several aspects of autonomic disease and do not as
yet forego the hope that hypertension may one day be treated pharma
cologically might be interested in paging through this book. Finally,
medical students should look to this book for basic descriptions of syn
aptic mechanisms, transmitter function, peristaltic motion, and gastro
intestinal processes.
We would be remiss if we did not at this time express our thanks to
the many people who contributed to the creation of this volume. The
editors wish to include in this list, of course, our colleagues, who with
us are the authors. We should also thank our staffs, which include Mary
Ann Jurgus in Chicago and Blockaden Machen in Kurume. Also, our
thanks are due to the administrations of Loyola University of Chicago and
its Stritch School of Medicine and of Kurume University Medical College,
who made our past research as well as this endeavor possible. Special
thanks are due to Dr. Charles Visokay of Karger Publishers, who helped
us in organizing the planning sessions, and to Mr. Kirk Jensen, Senior
Editor of Plenum Publishing Corporation, and his firm for their help and
for their patience and support during the long process of creating and
producing this book.
Alexander G. Karczmar, K. Koketsu, and S. Nishi
Maywood, Illinois, and Kurume, Japan
Contents
I. mSTORY AND ANATOMICAL BASES OF GANGLIONIC
AND ENTERIC TRANSMISSION
Chapter 1. Historical Development of Concepts of Ganglionic
Transmission 3
Alexander G. Karczmar
I. Anatomical and Morphological Aspects of Past Ganglionic Research 3
II. Neurotransmitters 9
III. Neuropharmacology and Neurophysiology 15
IV. Unanswered Questions 17
References 18
Chapter 2. Anatomy, Histology, and Electron Microscopy of
Sympathetic, Parasympathetic, and Enteric Neurons 27
Gordon M. Lees
I. Introduction 27
II. Parasympathetic and Sympathetic Ganglia 28
A. Gross Anatomical Considerations 28 B. Convergence and Divergence 30
C. Origin of Fibers That Form Postganglionic Nerves from Superior Cervical Ganglia
32 D. Innervation of the Gallbladder 34 E. Innervation of the Urinary Bladder
34 F. Ultrastructural Considerations of Principal Sympathetic Ganglion Cells 35
III. Chromaffin Cells. Small Intensely Fluorescent Cells. Small Granule-Containing Cells.
Interneurons. Paraneurons. and Paraganglia 37
IV. Enteric Nervous System 39
A. Extrinsic Nerves 39 B. Intrinsic Nerves 41 C. Glial Cells 47
V. Peptides in Other Autonomic Ganglia 48
References 50
xi
