New Concepts in Neurotransmitter Regulation: Proceedings of a Symposium on Drug Abuse and Metabolic Regulation of Neurotransmitters held in La Jolla, Californina, in July 1972

319 Pages·1973·20.65 MB·English

by  Wallace Dairman (auth.)

NEW CONCEPTS IN
NEUROTRANSMITIER REGULATION
NEW CONCEPTS IN
NEUROTRANSMITTER
REGULATION
Proceedings of a Symposium on Drug Abuse and Metabolic Regulation
of Neurotransmitters held in La Jolla, California, in July 1972
EDITED BY
ARNOLD J. MANDELL
Department of Psychiatry
School of Medicine
University of California at San Diego
La Jolla, California
PLENUM PRESS • NEW YORK-LONDON • 1973
Library of Congress Catalog Card Number 73-79222
ISBN -13 :97 8-1-4613-4576-3 e-ISBN -13 :97 8-1-4613-4574-9
001: 10.1007/978-1-4613-4574-9
© 1973 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1973
A Divis on of Plenum Publishing Corporation
227 West 17th Street, New Yark, N. Y. 10011
United Kingdom edition published by Plenum Press, London
A Division of Plenum Publishing Company, Ltd.
Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London,
NW10 6SE, England
All rights reserved
No part of this publication may be reproduced in any form without
written permission from the publisher
PREFACE
Historically, the development of biological science has
proceeded from the anatomy to the physiology of particular systems.
Knowledge about neurotransmitters in the brain has evolved from the
discovery of the compounds per set through the elucidation of their
biosynthetic and degradative pathways, and finally to the current
focus, the regulation of these processes.
Regulation in a biological system implies the capacity to
respond to perturbations. The introduction of standard and speci
fiable disturbances in a biological system followed by examination
of the mechanisms involved in response, i.e. that dampen and/or
cancel the induced changes, has proved to be a successful way to
elucidate regulatory mechanisms.
Psychotropic drugs have been most useful to students of regula
tory mechanisms in that calvarial prisoner, the brain, for they
allow prospective manipulation of variables like dosage and time.
Those of us interested in the biological substrata of behavior are
especially excited that disturbance induced by drugs leaves the
organism intact and behaving, and we can observe behavioral
correlates.
The pharmacological strategy is, of course, not unique to
brain scientists. The relationship between psychotropic drugs
and our emerging knowledge of neurotransmitter regulation is, for
example, akin to the development of anticancer agents in company
with the uncovering of many mysteries of molecular biology.
Working in this field, we are blessed with a very important
impetus to our basic research, namely, relevance. At least two
areas of human suffering justify our continued efforts: psycho
pathology and the promise of effective treatment thereof with drugs,
and the abuse of and addiction to drugs affecting the central nervous
system. Both areas will benefit ultimately from studies of the
regulation of the biosynthesis and the effects of neurotransmitters.
We see neuropharmacology as the basic science most relevant to
psychiatry, and examples of the best current work in the field
are to be found in these pages.
v
vi PREFACE
We were delighted that the Center for Studies of Drug Abuse
and Narcotics Addiction, and Drs. Bunney, Peterson, Braude, Szara,
and Nuite of the National Institute of Mental Health saw fit to aid
the private foundation, Friends of Psychiatric Research of San
Diego, Inc. in sponsoring a symposium on this important and timely
work. We were also very pleased that all the invited guests saw
fit to take time from their busy and productive schedules of
activity to deliver papers of outstanding quality.
Thanks are also in order to Drs. Suzanne Knapp, Ronald
Kuczenski, and David Segal, whose work and effort helped create
the local scientific base for the proceedings; to Noelle Cason
for immeasurable help in planning and arranging the meeting; and
to Linda Bailey and Barbara Blomgren for their assistance with
editing and production.
I think we all had a stimulating and delightful time together.
I hope a bit of this feeling pervades the book.
Arnold J. Mandell
La Jolla
February, 1973
CONTRIBUTORS
GEORGE K. AGHAJANIAN, Departments of Pharmacology and Psychiatry,
School of Medicine, Yale University, New Haven, Conn.
JAMES P. BENNETT, Department of Pharmacology, School of Medicine,
The Johns Hopkins University, Baltimore, Maryland
RICHARD BJUR, Department of Pharmacology, School of Medicine, Uni
versity of Colorado, Denver, Colorado
FLOYD E. BLOOM, Laboratory of Neuropharmacology, National Institute
of Mental Health, St. Elizabeth's Hospital, Washington, D.C.
FRANK C. BOVE, Department of Pharmacology, School of Medicine, Uni
versity of Colorado, Denver, Colorado
BENJAMIN S. BUNNEY, Department of Psychiatry, School of Medicine,
Yale University, New Haven, Connecticut
GILLES CLOUTIER, Department of Pharmacology, School of Medicine, Uni
versity of Colorado, Denver, Colorado
ERMINO COSTA, Laboratory of Preclinical Pharmacology, National Inst.
of Mental Health, St. Elizabeth's Hospital, Washington, D.C.
GALE L. CRAVISO, Department of Pharmacology, School of Medicine,
New York University, New York, New York
WALLACE DAIRMAN, The Roche Institute of Molecular Biology, Nutley,
New Jersey
JACQUES GLOWINSKI, Laboratory of Molecular Biology, College of
France, Paris, France
AVRAM GOLDSTEIN, Department of Pharmacology, School of Medicine,
Stanford University, Stanford, California
ALESSANDRO GUIDOTTI, Laboratory of Preclinical Pharmacology, Nat'l
Inst. of Mental Health, St. Elizabeth's Hosp., Washington, D.C.
MICHEL HAMON, Laboratory of Molecular Biology, College of France,
Paris, France
vii
viii CONTRIBUTORS
FRANCIS HERY, Laboratory of Molecular Biology, College of France,
Paris, France
ING K. HO, Langley Porter Neuropsychiatric Institute, San Francisco,
California
BARRY J. HOFFER, Laboratory of Neuropharmacology, National Institute
of Mental Health, St. Elizabeth's Hosp., Wash., D.C.
LESLIE L. IVERSEN, Department of Pharmacology, University of
Cambridge, England
IRWIN J. KOPIN, Laboratory of Clinical Science, National Institute
of Mental Health, Bethesda, Maryland
MICHAEL J. KUHAR, Department of Psychiatry, School of Medicine,
Yale University, New Haven, Connecticut
SALOMON Z. LANGER, Institute of Pharmacological Research, Buenos
Aires, Argentina
WILLIAM J. LOGAN, Department of Neurology, School of Medicine, The
University of Virginia, Charlottesville, Virginia
HORACE H. LOH, The Langley Porter Neuropsychiatric Institute,
San Francisco, California
ARNOLD J. MANDELL, Department of Psychiatry, School of Medicine,
University of California at San Diego, La Jolla, Ca.
EDITH G. McGEER, Department of Psychiatry, University of British
Columbia, Vancouver, B. C., Canada
PAUL L. McGEER, Department of Psychiatry, University of British
Columbia, Vancouver, B. C., Canada
CHARLENE A. McQUEEN, Department of Pharmacology, School of Medicine,
New York University, New York, New York
JOSE M. MUSACCHIO, Department of Pharmacology, School of Medicine,
New York University, New York, New York
FRANZ OESCH, Department of Pharmacology, Biocenter of the University,
Basel, Switzerland
CANDACE B. PERT, Department of Pharmacology, School of MediCine,
The Johns Hopkins University, Baltimore, Maryland
CONTRIBUTORS ix
FREDERICK E. SCHON, Physiological Laboratorv, The University of
Cambridge, England
GEORGE R. SIGGINS, Laboratory of Neuropharmacology, National Insti
tute of Mental Health, St. Elizabeth's Hosp., Wash., D.C.
SOLOMON H. SNYDER, Departments of Pharmacology and Psychiatry,
School of Medicine, The Johns Hopkins Univ., Baltimore, Md.
HANS THOENEN, Department of Pharmacology, Biocenter of the University,
Basel, Switzerland
E. LEONG WAY, The Langley Porter Neuropsychiatric Institute,
San Francisco, California
NORMAN WEINER, Department of Pharmacology, School of Medicine,
University of Colorado, Denver, Colorado
HENRY I. YAMAMURA, Biomedical Laboratory, Edgewood Arsenal, Edgewood,
Maryland
CONTENTS
Preface •••••• v
Arnold J. Mandell
Contributors . . . . . . . . . . . . . . . . . . . . vii
NEUROTRANSMITTER REGULATION AND ENZYME SYNTHESIS
Multiple Measures of Compensatory Adaptation
in Catecholamine Biosynthesis • • • • 1
Wallace Dairman
Control of Synthesis, Transport, and Release of Dopamine-
Beta-Hydroxylase and Tyrosine Hydroxylase ••• • 21
Irwin J. Kopin
New Enzyme Synthesis as a Long-Term Adaptation to
Increased Transmitter Utilization • • • • 33
Hans Thoenen and Franz Oesch
NEUROTRANSMITTER REGULATION AND ENZYME ACTIVITY
Some characteristics of Brain Tyrosine Hydroxylase 53
Edith G. McGeer and Paul L. McGeer
Tyrosine Hydroxylase: Subcellular Distribution and
Molecular and Kinetic Characteristics of the
Different Enzyme Forms •••••••• 69
Jos~ M. Musacchio, Charlene A. Mcqueen, and
Gale L. Craviso
Norepinephrine Biosynthesis in Relation to Neural
Activation • • • • • • • • • • • 89
Norman Weiner, Frank C. Bove, Richard Bjur,
Gilles Cloutier, and Salomon Z. Langer
xi
xii CONTENTS
NEW APPROACHES TO NEUROTRANSMITTER REGULATION
Use of Single Unit Recording in Correlating Transmitter
Turnover with Impulse Flow in Monoamine
Neurons • • • • • • • • • • • • • • • • • 115
George K. Aghajanian. Benjamin S. Bunney. and
Michael J. Kuhar
The Role of 3'.5'-Cyclic Adenosine Monophosphate in the
Regulation of Adrenal Medullary Function 135
Ermino Costa and Alessandro Guidotti
The Use of Autoradiographic Techniques for the
Identification and Mapping of Transmitter-
Specific Neurones in CNS • • • • 153
Leslie L. Iversen and Frederick E. Schon
Neuronal Uptake of Neurotransmitters and Their
Precursors: Studies with "Transmitter"
Amino Acids and Choline • • • • • • • • 195
Solomon H. Snyder. Henry 1. Yamamura. Candace B. Pert.
William J. Logan. and James P. Bennett
MULTIVARIATE CONSIDERATIONS IN NEUROTRANSMITTER REGULATION
Central Noradrenergic Receptors: Localization. Function.
and Molecular Mechanisms •••••••••••• 223
Floyd E. Bloom. Barry J. Hoffer. and George R. Siggins
Regulation of 5-HT Synthesis in Central Serotonergic
Neurons . • . . • • . .•..... 239
Jacques Glowinski. Michel Hamon. and Francis Hery
Redundant Macromolecular Mechanisms in Central Synaptic
Regulation ...........•.•.... 259
Arnold J. Mandell
OPIATE DRUG EFFECTS AND NEUROTRANSMITTER REGULATION
Relation of Brain Serotonin to the Inhibition and Enhance-
ment of Morphine Tolerance and Physical Dependence • • 279
E. Leong Way. Ing K. Ho. and Horace H. Loh
Recent Studies on the Binding of Opiate Narcotics to
Possible Receptor Sites • • • • • • • • • 297
Avram Goldstein
Index 311