Peptides in Neurobiology

477 Pages·1977·14.508 MB·English

by  Berta Scharrer (auth.), Harold Gainer (eds.)

Peptides in
Neurobiology
CURRENT TOPICS IN NEUROBIOLOGY
Series Editors:
Samuel H. Barondes
University of California, San Diego
La Jolla, California
and
Floyd Bloom
The Salk Institute
La Jolla, California
Tissue Culture of the Nervous System
Edited by Gordon Sato
Neuronal Recognition
Edited by Samuel H. Barondes
Peptides in Neurobiology
Edited by Harold Gainer
A Continuation Order Plan is available for this series. A continuation order will bring
delivery of each new volume immediately upon publication. Volumes are billed only upon
actual shipment. For further information please contact the publisher.
Peptides in
Neurobiology
Edited by
Harold Gainer
National Institute of Child Health
and Human Development
Bethesda, Maryland
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Peptides in neurobiology.
(Current topics in neurobiology)
Includes bibliographies and index.
1. Neuroendocrinology. 2. Pep tides. 3. Hypothalamic hormones. 4. Central nervous
system. I. Gainer, Harold. [DNLM: 1. Peptides. 2. Neurochemistry. WI CU82P v. 3
/WLl 04 P4 24)
QP356.4.P36 591.1'88 76-54766
ISBN-13: 978-1-4613-4132-1 e-ISBN-13: 978-1-4613-4130-7
DOT: 10.1007/978-1-4613-4130-7
First Printing-May 1977
Second Printing-April 1979
© 1977 Plenum Press, New York
Softcover reprint of the hardcover I st edition 1977
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
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
Contributors
Jeffery L. Barker, Behavioral Biology Branch, National Institute of Child Health
and Human Development, National Institutes of Health, Bethesda, Mary
land 20014.
Michael J. Brownstein, Section on Pharmacology, Laboratory of Clinical Sci
ence, National Institute of Mental Health, Bethesda, Maryland 20014.
Robert E. Carraway, Laboratory of Human Reproduction and Reproductive
Biology and Department of Physiology, Harvard Medical School, Boston,
Massachusetts.
Ian M. Cooke, Laboratory of Sensory Sciences and Department of Zoology,
University of Hawaii, Honolulu, Hawaii 96822.
D. de Wied, Rudolf Magnus Institute for Pharmacology, Medical Faculty, Uni
versity of Utrecht, Vondellaan 6, Utrecht, The Netherlands.
P.O. Edminson, Department of Neurochemistry, The University Psychiatric
Clinic, Vinderen, Oslo 3, Norway.
Nora Frontali, Istituto Superiore di Sanita, Viale Regina Elena, 299, Rome,
Italy.
Harold Gainer, Section on Functional Neurochemistry, Behavioral Biology
Branch, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland 20014.
W.H. Gispen, Rudolf Magnus Institute for Pharmacology, Medical Faculty, Uni
versity of Utrecht, Vondellaan 6, Utrecht, The Netherlands.
Werner A. Klee, Laboratory of General and Comparative Biochemistry, National
Institute of Mental Health, Bethesda, Maryland 20014.
Susan E. Leeman, Laboratory of Human Reproduction and Reproductive Biol
ogy and Department of Physiology, Harvard Medical School, Boston,
Massachusetts.
Y. Peng Loh, Section on Functional Neurochemistry, Behavioral Biology Branch,
National Institute of Child Health and Human Development, National Insti
tutes of Health, Bethesda, Maryland 20014.
Neville Marks, New York State Research Institute for Neurochemistry and Drug
Addiction, Ward's Island, New York 10035.
v
vi Contributors
Edmund A. Mroz, Laboratory of Human Reproduction and Reproductive Biol
ogy and Department of Physiology, Harvard Medical School, Boston,
Massachusetts.
K.L. Reichelt, Department of Neurochemistry, The University Psychiatric Clinic,
Vinderen, Oslo 3, Norway.
Yosef Sarne, Department of Behavioral Biology, Technion Medical School,
Haifa, Israel.
Berta Scharrer, Department of Anatomy, Albert Einstein College of Medicine,
1300 Morris Park Avenue, Bronx, New York 10461.
Stanley Stein, Roche Institute of Molecular Biology, Nutley, New Jersey
07110.
Ludwig A. Sternberger, Immunology Branch, Edgewood Arsenal, Maryland
21010.
Eugene Straus, Solomon A. Berson Research Laboratory, Veterans Administra
tion Hospital, Bronx, New York 10468.
Rosalyn S. Yalow, Mt. Sinai School of Medicine, The City University of New
York, New York.
Preface
Elucidation of the important roles played by peptides as hypothalamic-adenohypo
physeal releasing factors, or regulatory hormones, has in recent years led to the
recognition that peptides may also be of significance as intercellular messengers
in other regions of the nervous system. In this regard, it is interesting that Sub
stance P, which has been proposed as a putative neurotransmitter in the spinal
cord, was rediscovered by Leeman and her co-workers during their search for
the corticotropin-releasing factor in the hypothalamus. Indeed, with the wide
spread availability and use of radioimmunoassay techniques, it has become ap
parent that various "hypothalamic releasing factors" are localized in extrahypo
thalamic areas of the central nervous system as well. This book represents an
expression of the belief that the impact on neurobiology of research into neuro
peptides will be comparable to, if not greater than, the recent achievements
obtained with the biogenic amines. As already appears to be the case, future inves
tigations on brain pep tides will undoubtedly uncover a host of new transmitter
candidates, with obvious implications for neuropharmacology. Perhaps the most
dramatic developments in this field have been the discoveries of the endogenous
opiate peptides (enkephalin and endorphin), and the profound physiological and
behavioral effects of specific peptides. The functions and mechanisms of action of
these peptides are not entirely clear at present, but expectations are high that the
answers to these questions will inaugurate a conceptual revolution in neurobiol
ogy. Thus, what had once been considered the exclusive province of neuroendo
crinology has now emerged as a major issue in neurobiology as a whole.
The principal aim of this book is to provide the neurobiological commu
nity with a baseline of information and perspectives in the rapidly moving field
of neuropeptides. Some of the central questions that have been addressed are:
What evidence exists to suggest that peptides are involved in the control of the
nervous system? Are peptides credible candidates as neurotransmitters and neuro
modulators? If so, how do they differ .from the conventional neurotransmitter
agents? Do peptidergic neurons exhibit distinctive cell biological properties
vis-a-vis "conventional" neurons? What are the roles of proteolytic enzymes in
peptide biosynthesis and inactivation? Finally, how do peptides influence or
mediate behavior? Detailed considerations of the neuroendocrine functions of the
vii
viii Preface
releasing factors and of peptides such as nerve growth factor have been omitted,
primarily because they have already been dealt with extensively in the literature.
Instead, the principal focus has been directed at the strategies and tactics that have
been found useful in the characterization of neuropeptides and their functions. In
addition to providing a systematic exposition of peptides in neurobiology, the
authors have proposed various models and hypotheses, with the expectation that
they will provoke new ideas and experimental challenges.
This book is organized into four major areas: (1) biochemical methodology,
(2) the anatomical localization and biochemical analysis of various biologically ac
tive peptides in the central nervous system, (3) the metabolism of peptides, and
(4) the physiological, pharmacological, and behavioral effects of peptides. Over
lap of material between the chapters has been kept to a minimum by having each
of the authors refer to relevant sections in other chapters. In her historical in
troduction, Scharrer discusses the conceptual movement towards peptides in
neurobiology. Since the biochemical analysis of peptides is to some extent unique
and particularly problematic, several chapters have been devoted almost exclu
sively to methodology. The chapter by Stein deals with the application of fluores
cent techniques to the separation and detection of peptides, while Straus and
Yalow discuss in detail the potential pitfalls and benefits in the use of the powerful
technique of radioimmunoassay. In addition to describing immunocytochemical
methodology, Sternberger also reviews the current state of knowledge with regard
to the cellular localization of peptides in the central nervous system. Leeman,
Mroz, and Carraway discuss their extensive work on Substance P and neurotensin
in the context of a general paradigm for the analysis of peptides in nervous tissue.
The chapter by Brownstein considers the regional localization of biologically ac
tive peptides in the central nervous system, and discusses the difficulties in in
terpretation of much of the data in this area. Three chapters are concerned with the
metabolism of neuropeptides, their biosynthesis by "synthetase" (Reichelt and
Edminson) and by ribosomal mechanisms (Gainer, Loh, and Sarne) , and
their inactivation in nervous tissue (Marks). The study of biologically active
peptides in invertebrate nervous systems has been an active field for some time.
Since neurobiologists are generally unfamiliar with this work, a chapter devoted
entirely to invertebrate neuropeptides was written by Frontali and Gainer. In addi
tion, three other chapters describe work in which invertebrate nervous systems
have provided valuable models for the examination of the general properties of
peptidergic neurons. Among these are the chapters by Barker and by Cooke, who
discuss experiments in which intracellular electrical recordings were made from
invertebrate peptidergic neurons and nerve terminals, respectively. The rela
tionship of these data to vertebrate studies is also treated in these chapters. Klee's
chapter on the endogenous opiate peptides attempts to place this exciting field in
historical context. Finally, the effects of various peptide hormones and their ana
logues on behavior is presented in a chapter by de Wied and Gispen.
The study of peptides in neurobiology is still only in its infancy. However,
sufficient evidence exists at present to indicate that within this class of molecules,
there resides a cornucopia of surprises, joys, and clues to brain function for
Preface ix
neurobiologists with inclinations from the molecular to the behavioral level. It is
hoped that this volume will be the first of many to document the progress of pep
tides in neurobiology.
Harold Gainer
Bethesda, Maryland
Contents
Chapter 1
Peptides in Neurobiology: Historical Introd uction
Berta Scharrer
1. The Neurosecretory Neuron and the Concept of Neurosecretion .... 1
2. The Hypothalamic Origin of the Posterior Lobe Hormones ........ 3
3. The Hypothalamic Control of the Adenohypophysis .............. 4
4. Nonhormonal Neurosecretory Signals to Endocrine and Nonendocrine
Effector Cells ............................................. 5
5. Peptidergic Interneuronal Communication ...................... 6
6. Conclusion ............................................... 6
7. References ............................................... 7
Chapter 2
Application of Fluorescent Techniques to the Study
of Peptides
Stanley Stein
1. Introduction 9
2. Preparation of Materials and Equipment ....................... 11
3. Isolation of Peptides from Tissues ............................ 12
4. Separation and Detection of Peptides .......................... 13
4.1. Noncolumn Methods for Free Peptides .................... 13
4.2. Column Methods for Free Peptides ....................... 14
4.3. Noncolumn Methods for Prelabeled Peptides ............... 19
4.4. Column Methods for Prelabeled Peptides .................. 23
5. Applications .............................................. 24
5.1. Isolation of Pure Peptides ............................... 24
5.2. Quantitative Analysis .................................. 26
5.3. Physiological Studies .................................. 28
5.4. Chemical Characterization .............................. 30
xi