Hormonal Proteins and Peptides Editor CHOH HAO LI The Hormone Research Laboratory University of California San Francisco, California Vol I 1973 Vol II 1973 Vol III 1975 Vol IV Growth Hormone and Related Proteins 1977 Vol V Lipotropin and Related Peptides 1977 Vol VI Thyroid Hormones 1978 Vol VII Hypothalamic Hormones 1979 Vol VIII Prolactin 1980 Vol IX Techniques in Protein Chemistry Vol X β-Endorphin I ΙΟΙ I M OW L PROTEINS A ND P E P T I D ES Edited by CHOH HAO LI The Hormone Research Laboratory University of California San Francisco, California VOLUME X /3-Endorphin 1981 ACADEMIC PRESS A Subsidiary of Harcourt Brace Jovanovich, Publishers New York London Toronto Sydney San Francisco COPYRIGHT © 1981, BY ACADEMIC PRESS, INC. ALL RIGHTS RESERVED. NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL, INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM, WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. Ill Fifth Avenue, New York, New York 10003 United Kingdom Edition published by ACADEMIC PRESS, INC. (LONDON) LTD. 24/28 Oval Road, London NW1 7DX Library of Congress Cataloging in Publication Data Main entry under title: β-endorphin. (Hormonal proteins and peptides; v. 10) Includes bibliographies and index. 1. Endorphins. I. Li, Choh Hao, Date. II. Series. QP572.P77H67 vol.10 [QP951.E5] 599.0Γ927 [615V7822] ISBN 0-12-447210-9 81-10994 AACR2 PRINTED IN THE UNITED STATES OF AMERICA 81 82 83 84 9 8 7 6 5 4 3 2 1 Contributors Numbers in parentheses indicate the pages on which the authors' contributions begin. HUDA AKIL (171), Mental Health Research Institute, Department of Psy­ chiatry, University of Michigan, Ann Arbor, Michigan 48109 JACK D. BARCHAS (293), Department of Psychiatry and Behavioral Sci­ ences, Stanford University School of Medicine, Stanford, California 94305 PHILIP A. BERGER (293), Department of Psychiatry and Behavioral Sci­ ences, Stanford University School of Medicine, Stanford, California 94305 GUY BOILEAU (65), Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada DON H. CATLIN (311), Departments of Medicine and Pharmacology, Uni­ versity of California, Los Angeles, California 90024 MICHEL CHRÉTIEN (65), Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada ROBERT H. GERNER (311), Department of Psychiatry, University of Cali­ fornia, Los Angeles, California 90024 DAVID A. GORELICK (311), Brentwood Veterans Administration Medical Center, Los Angeles, California 90073 LASZLO GRAF (35), Institute for Drug Research, Budapest, Hungary JOHN W. HOLADAY (203), Department of Medical Neurosciences, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C. 20012 AGNES KENESSEY (35), Institute for Drug Research, Budapest, Hungary CHOH HAO LI (1), The Hormone Research Laboratory, University of California, San Francisco, California 94143 HORACE H. LOH (89, 203), School of Medicine, Department of Phar­ macology, University of California Medical Center, San Francisco, Cal­ ifornia 94143 NABIL G. SEIDAH (65), Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada ix χ CONTRIBUTORS ANDREW P. SMITH (89), School of Medicine, Department of Pharmacol­ ogy, University of California Medical Center, San Francisco, California 94143 STANLEY J. WATSON (171), Mental Health Research Institute, Depart­ ment of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109 E. LEONG WAY (339), School of Medicine, Department of Pharmacology, University of California, San Francisco, California 94143 Prefaiée The discovery of a hormone or a biologically active compound may result from two approaches: biological and chemical. Both corticotropin (ACTH) and melanotropins (a- and /3-MSH) were discovered by the bio­ logical approach and were deduced from observations of the effect of hypophysectomy and subsequent replacement therapy in the hypophysec- tomized animal. The chemical approach involves isolating a chemical entity from its natural source and investigating its biological activity after it has been determined to be a pure substance. One outcome of this approach was the discovery of β-lipotropin (/3-LPH) in 1964. In the course of improving the method for the isolation of ACTH from sheep glands, our laboratory, in collaboration with Y. Birk, obtained a new polypeptide that differed com­ pletely from all other known pituitary hormones. Its biological activity was tested after it had been characterized chemically. The amino acid sequence of β-LPH was proposed in 1965. The discovery of /3-endorphin also was achieved through the chemical approach. Since the early 1970s, with W. Danho and D. Chung, we have been investigating various hormones from camel pituitaries. When the camel pituitary extract was submitted to fractionation on ion-exchange resin chromatography in the same manner as for the isolation of sheep /3-LPH with Chung, we were not able to find camel /3-LPH, but we did isolate a 31-amino acid peptide with very little lipolytic activity. This was achieved in early 1974. Subsequently, the primary structure of the un- triakontapeptide was established to be the sequence (residues 61-91) of the COOH-terminal 31-amino acids in the sheep /3-LPH molecule. In comparing the structures of methionine-enkephalin [/3-LPH-(61-65)] with this new peptide, it was obvious that it could have morphine-like activity. It turned out that the new peptide was much more potent than methionine- enkephalin in both in vivo and in vitro assay systems. It was named jS-endorphin (β-ΕΡ). In 1976, human β-ΕΡ was isolated, sequenced, and xi xii PREFACE synthesized. Since then, a great deal of research activity has been cen­ tered on β-ΕΡ. This volume is devoted exclusively to the chemistry, biology, and clini­ cal studies of this opioid peptide. The first chapter, by Li, presents the structure-activity relationship of β-ΕΡ by synthetic approach. In the sec­ ond chapter, Graf and Kenessey consider proteinases involved in the generation of opioid peptides, including β-ΕΡ from β-LPH. This is fol­ lowed by a short review on biosynthesis of β-ΕΡ written by Boileau, Seidah, and Chrétien. In Chapter 4, Smith and Loh consider in detail the opiate receptor. The anatomy of β-ΕΡ-containing structures in pituitary and brain is discussed by Watson and Akil in Chapter 5. Holaday and Loh present a comprehensive review of the neurobiology of β-ΕΡ and related peptides in Chapter 6. The clinical studies of β-ΕΡ are discussed by Berger and Barchas in Chapter 7 and by Catlin, Gorelick, and Gerner in Chapter 8. In the final chapter of this volume, Way presents his observa­ tions on the historical aspects of opiate-peptide discoveries (especially in the field of narcotic antagonists), in connection with his mentor Chauncey Leake. As always, I am indebted to the staff of Academic Press for their work in the production of this volume. Choh Hao Li Contents of Previous Volumes Volume I 1. The Chemistry of Glycoproteins Richard J. Winzler 2. The Chemistry of Pituitary Thyrotropin John G. Pierce, Ta-Hsiu Liao, and Robert B. Carlsen 3. The Chemistry of the Interstitial Cell-Stimulating Hormone of Ο Pituitary Origin Harold Papkoff 4. The Biology of Pituitary Interstitial Cell-Stimulating Hormone M. R. S ai ram and Choh Hao Li 5. Chemistry of Human Chorionic Gonadotropin Om P. Bahl 6. Chemistry and Biosynthesis of Thyroid Iodoproteins G. Salvatore and H. Edelhoch Author Index—Subject Index Volume II 1. The Structure and Function of Adrenocorticotropin J. Ramachandran 2. Gastrointestinal Hormones Miklos Bodanszky xiii XIV CONTENTS OF PREVIOUS VOLUMES 3. Peptide Synthesis: A Review of the Solid-Phase Method Johannes Meienhofer Author Index—Subject Index Volume III 1. The Chemistry of Human Pituitary Growth Hormone: 1967-1973 Choh Hao Li 2. Immunochemical and Biological Studies with Antisera to Pituitary Growth Hormones T. Hayashida 3. Clinical Studies of Human Growth Hormone in Children with Growth Problems Roberto F. Escamilla 4. Acromegaly John A. Linfoot, Claude Y. Chong, John H. Lawrence, James L. Born, Cornelius A. Tobias, and John Lyman 5. Endocrinology and Herbert M. Evans Leslie L. Bennett Author Index—Subject Index Volume IV Growth Hormone and Related Proteins 1. Bioassay of Pituitary Growth Hormone Choh Hao Li 2. Growth Hormone and the Regulation of Lipolysis A. Jagannadha Rao and J. Ramachandran 3. The Chemistry of Human Choriomammotropin Thomas A. Bewley 4. Control of Prolactin Secretion James A. Clemens and Joseph Meites CONTENTS OF PREVIOUS VOLUMES XV 5. Hypophysectomy and Philip E. Smith James H. Leathern Author Index—Subject Index Volume V Lipotropin and Related Peptides 1. The Chemistry of Melanotropins Choh Hao Li 2. β-Endorphin: A New Biological Active Peptide from Pituitary Glands Choh Hao Li 3. Lipotropins M. Chrétien and M. Lis 4. The Neurophysins Β. T. Pickering and C W. Jones 5. Separation Methods and Arne Tiselius Jerker Ρ or at h Author Index—Subject Index Volume VI Thyroid Hormones 1. Chemistry of Human Pituitary Thyrotropin M. R. S air am and Choh Hao Li 2. Thyroid Hormones and Analogs, I. Synthesis, Physical Properties, and Theoretical Calculations Eugene C. Jorgensen 3. Thyroid Hormones and Analogs, II. Structure-Activity Relationships Eugene C. Jorgensen 4. The Mechanism of Thyroxine Action Mary Ragan Dratman