Table Of ContentSOMATOSTATIN
Basic and Clinical Status
SERONO SYMPOSIA, USA
Series Editor: James Posillico
SOMATOSTATIN: Basic and Clinical Status
Edited by Seymour Reichlin
ACROMEGALY: A Century of Scientific and Clinical Progress
Edited by Richard J. Robbins and Shlomo Melmed
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SOMATOSTATIN
Basic and Clinical Status
Edited by
Seymour Reichlin
Tufts University
Boston, Massachusetts
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging in Publication Data
International Conference on Somatostatin (1986: Washington, D.C.)
Somatostatin: basic and clinical status.
"Proceedings of the International Conference on Somatostatin, held May 6-8, 1986 in Washington,
D.C."-T.p. verso.
"Serono Symposia, USA"-Cover.
Includes bibliographies and indexes.
1. Somatostatin-Congresses. I. Reichlin, Seymour, 1924- . II. Serono Symposia, USA. III. Title.
[DNLM: 1. Somatostatin-congresses. WK 515 15875 1986]
QP572.S59158 1986 612'.015756 87-7923
ISBN 978-1-4684-5328-7 ISBN 978-1-4684-5326-3 (eBook)
DOI 10.1007/978-1-4684-5326-3
Proceedings of the International Conference on Somatostatin,
held May 6-8, 1986, in Washington, D.C.
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taken to maintain the accuracy of the information contained in the volume. However, neither Plenum
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© 1987 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1987
Softcover reprint of the hardcover 1st edition 1987
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SCIENTIFIC COMMITTEE
Seymour Reichlin, M.D., Ph.D., Chai~an
Tufts University
Boston, MA
John Gerich, M.D.
Mayo Clinic
Rochester, MN
Richard H. Goodman, M.D., Ph.D.
Tufts University
Boston, MA
Yogesh C. Patel, M.D., Ph.D.
McGill University
Montreal, Canada
Roger Unger, M.D.
University of Texas
Dallas, TX
Klaus-Henning Usadel, M.D.
University of Heidelberg
Mannheim, West Germany
Tadataka Yamada, M.D.
University of Michigan
Ann Arbor, MI
ORGANIZING SECRETARIES
Ching Lau, Ph.D.
James T. Posillico, Ph.D.
Serono Symposia, USA
Randolph, MA
v
PREFACE
The discovery of hypothalamic factors that inhibited growth hormone
secretion and of pancreatic factors that inhibited insulin secretion were
the first clues to the existence of somatostatin. During the course of
efforts to isolate growth hormone releasing factor, Krulich, McCann and
Dhariwal found that hypothalamic extracts contained a potent inhibitor of
growth hormone secretion. They postulated that growth hormone secretion
was under a dual control system, one inhibitory and the other excitatory
(I) . In studies being carried out at about the same time, Hellman and
Lernmark found a factor in pancreatic extracts that inhibited insulin
secretion (2). They postulated that islet cell function was regulated by
local hormonal factors. With the isolation and chemical characterization
of somatostatin by Brazeau and colleagues (3), and the availability of
relatively large amounts of the synthetic peptide for research, it has
been possible to demonstrate that both predictions were true. Subsequent
work revealed that somatostatin, as initially isolated (somatostatin 14),
was but one of several related peptides, part of a multigene family, with
tissue specific processing. Many of the details of biosynthesis and
genetic control have been worked out, and this molecule has served many
workers as a model gut-brain peptide for detailed study. The peptides are
widely distributed in tissues and exert an extraordinary range of effects
on most glandular secretions, both internal and external. Further, they
are present in the central nervous system where they exert a number of
physiological effects, and are present in the gastrointestinal tract where
they regulate a number of functions. The development of potent analogues,
with desirable properties, has led to new advances in the pharmacotherapy
of endocrine and gastrointestinal disease.
The extraordinary range of distribution and actions of the somato
statin family of peptides continues to stimulate intense scientific
interest and endeavor. Ongoing research has been reviewed in a number of
publications (4-9), and three international symposia have been held on
this topic: the first in 1977 in Freiberg, Germany (10), the second in
1981 in Athens, Greece (11), and the third in 1984 in Montreal, Canada
(12). This International Conference on Somatostatin, which took place in
Washington, DC, May 6-8, 1986, brought into focus the current status of
knowledge in major areas of somatostatin research. The topics covered
included the biosynthesis and processing of the peptide, mechanisms of
action, an assessment of the role of somatostatin in central nervous
system function and disease, the role of somatostatin in regulation of
gastrointestinal function, and a critical summary of the current thera
peutic uses of somatostatin and its analogues for the treatment of gastro
intestinal bleeding, acromegaly, diabetes, and functioning gastrointes
tinal tumors. In addition to presenting an up-to-the-minute understanding
of the current advances in somatostatin research, this volume captures the
sense of excitement felt by leading investigators in the field.
vii
REFERENCES
1. Krulich L, Dhariwal APS, McCann SM. Stimulatory and inhibitory
effects of purified hypothalamic extracts on growth hormone release
from rat pituitary in vitro. Endocrinology 1968; 83:783-90.
2. Hellman B, Lernmark A. Inhibition of the in vitro secretion of
insulin by an extract of pancreatic A-I cells. Endocrinology 1969;
84:1484-7.
3. Brazeau P, Vale W, Burgus R, et a!. Hypothalamic peptide that
inhibits the secretion of immunoreactive pituitary growth hormone.
Science 1973; 179:77-9.
4. Gerich JE. Somatostatin. In: Brownlee M, ed. Handbook of diabetes
mellitus. New York: Garland Publishing, Inc., 1981; 1:297-354.
5. Arimura A, Fishback JB. Somatostatin: regulation of secretion.
Neuroendocrinology 1981; 33:246-56.
6. Gottesman IS, Mandarino LJ, Gerich JE. Somatostatin. In: Cohen M,
Foa P, eds. Special topics in endocrinology and metabolism. New
York: Alan R. Liss, 1982:177-243.
7. Reichlin S. Somatostatin. In: Krieger DT, Brownstein MJ, Martin
JB, eds. Brain peptides. New York: John Wiley, 1983:711-52.
8. Reichlin S. Somatostatin. New Engl J Med 1983; 309:1495-1501,
1556-63.
9. Patel Y, Srikant C. Somatostatin. Annu Rev Physiol 1986; 48:551-67.
10. Gerich JE, Raptis S, Rosenthal J, eds. Somatostatin symposium.
Metabolism 1978; 28:1129-1469.
11. Raptis S, Rosenthal J, Gerich JE, eds. 2nd international symposium
on somatostatin. Germany: Attempto Verlag Tubingen GmbH, 1984.
12. Patel JC, Tannenbaum GS, eds. Somatostatin. New York: Plenum
Press, 1985.
viii
CONTENTS
I. BIOSYNTHESIS AND PROCESSING
1. Regulation and Diversity of Peptide Hormone Gene Expression. • 3
Joel F. Habener
2. Structure and Regulation of the Rat Somatostatin Gene 13
Jack E. Dixon, Timothy E. Hayes, Marie Tavianini,
Bernard A. Roos, and Ourania Andrisani
3. Regulation of Somatostatin Gene Expression by Cyclic AMP 21
Richard H. Goodman, Gail Mandel, Kevin A. Sevarino, and
Marc R. Montminy
4. Pep tides Derived from Mammalian Prosomatostatin • • • • • • • • 33
Robert Benoit
5. Expression of Preprosomatostatin in Foreign Cells:
Secretion of Mature Somatostatin by Yeast
(Saccharomyces Cerevisiae) ••••••• • • • • • • 51
Dennis Shields, Reza Green, Michael Schaber, and
Richard Kramer
6. Cotranslational and Posttranslational Proteolytic Processing
of Preprosomatostatin-I and Preprosomatostatin-II in
Intact Islet Tissue • • • • • • • • • • • • • • . 59
Bryan D. Noe, Robert B. Mackin, John K. McDonald,
Philip C. Andrews, Jack E. Dixon, and Joachim Spiess
7. Environmental Regulation of Neurotransmitter Phenotypic
Expression in Sympathetic Neurons • • • • • • • • 71
John A. Kessler
II. MECHANISMS OF ACTION
8. Side Chain Conformations of Somatostatin Analogs 'fuen Bound
to Receptors •••• • • • • • • • • • • • • • • • • 83
Ruth F. Nutt, C. Dylion Colton, Richard Saperstein, and
Daniel F. Veber
9. Somatostatin Receptor: Evidence for Functional and
Structural Heterogeneity • • • • • • • • • • • 89
Coimbatore B. Srikant and Yogesh C. Patel
ix
10. Structural Analysis of Somatostatin Receptors 103
John A. Williams and Christiane Susini
11. Mode of Action of Somatostatin in Islet B-Cells: Influence
on Glucose-. L-isoleucine- and Glyburide-Induced
Electrical Activity • • • • • • • • • • • • • • • • • III
Caroline S. Pace
12. Mechanisms by Which Somatostatin Inhibits Pituitary Hormone
Release • • • • • • • • • • • • 121
Agnes Schonbrunn and Bruce D. Koch
13. Molecular Mechanisms of Somatostatin Inhibition of Hormone
Release From AtT-20 Ce11s • • • • • • • • • • 137
Lawrence C. Mahan and Terry Reisine
III. ROLE OF SOMATOSTATIN IN NERVOUS SYSTEM FUNCTION AND
CONTROVERSIES IN SOMATOSTATIN RESEARCH
14. Regulation of Hypothalamic Somatostatin Secretion • 149
Richard Robbins. M.D.
15. Somatostatin and Behavior: Preclinical and Clinical
Studies ••••• 157
• ••0 •••••••
Charles B. Nemeroff. Thomas J. Walsh. and Garth Bissette
16. Physiological Significance of Somatostatin in Growth Hormone
Regulation • • • • • • • • • • • • • • • • • • • • • • 169
Gloria Shaffer Tannenbaum
17. Somatostatin and Depression ••••••••••• 183
David R. Rubinow. Robert M. Post. Candace Davis. and
Allen Doran
18. Cytoprotection by Somatostatins • • • • • • • • • • 193
K. H. Usadel. H. Kessler. G. Rohr. K. Kusterer.
K. D. Palitzsch. and U. Schwedes
19. Evidence for Paracrine Function of Somatostatin 201
Werner Creutzfeldt
20. Evidence for the Endocrine Role of Somatostatin • • • • • • •• 209
Volker Schusdziarra
IV. SOMATOSTATIN IN GASTROINTESTINAL FUNCTION
21. Gut Somatostatin 221
Tadataka Yamada
22. Regulation of Somatostatin Release From Dispersed Canine
Fundic D-Cells •••••••••• 229
Tsutomu Chiba. Jung Park. and Tadataka Yamada
23. Antral Somatostatin: A Paracrine Regulator of Gastrin
Secretion • • • • • • • • 239
G. M. Makhlouf. M.D •• Ph.D.
x
