Table Of ContentHormonal
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
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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]
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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
