Peptides in Neurobiology PDF
Preview Peptides in Neurobiology
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
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