handbooi( of neurochemistry - springer978-1-4615-7163-6/1.pdf · for neurochemistry and drug...
Post on 16-May-2018
229 Views
Preview:
TRANSCRIPT
HANDBOOI( OF NEUROCHEMISTRY
VOLUME IV
CONTROL MECHANISMS IN THE NERVOUS SYSTEM
HANDBOOK OF NEUROCHEMISTRY
Volume I
Volume 11 Volume III
Volume IV
Volume V
Volume VI
Volume VII
Edited by Abel Lajtha
Chemieal Arehitecture of the Nervous System
Struetural Neuroehemistry
Metabolie Reaetions in the Nervous System
Control Mechanisms in the Nervous System
Metabolie Turnover in the Nervous System
Alterations of Chemieal Equilibrium in the Nervous System
Pathologieal Chemistry of the Nervous System
HANDBOOI( OF NEUROCHEMISTRY
Edited by Abel Lajtha New York State Research Institute
for Neurochemistry and Drug Addiction Ward' s 1 sland
New York,New York
VOLUME IV
CONTROL MECHANISMS IN THE NERVOUS SYSTEM
9? PLENUM PRESS • NEW YORK- LONDON • 1970
Library of Congress Catalog Card Number 68·28097
SBN 306-37704-7
ISBN 978-1-4615·7165·0 ISBN 978-1-4615-7163·6 (eBook) DOI 10.1007/978-1·4615·7163·6
© 1970 Plen um Press, N ew Y ork Softcover reprint ofthe hardcover 1st edition 1970 A Division of Plenum Publishing Corporation
227 West 17th Street, New York, New York 10011
United Kingdom edition published by Plenum Press, London A Division of Plenum Publishing Company, Ltd_
Donington House, 30 Norfolk Street, London W_C. 2, England
All rights reserved
No part of this publication may be reproduced in any form without written permission from the publisher
Contributors to this volume :
R. Wayne Albers
Dorothea Aures
H. S. Bachelard
Arvid Carlsson
William G. Clark
Lynwood G. Clemens
E. Costa
David R. Curtis
Jacques Glowinski
Roger A. Gorski
Jack Peter Green
Laboratory of Neurochemistry, NationalInsti· tute of N eurological Diseases and Stroke, Na· tional Institutes of Health, Bethesda, Maryland (page 13)
Psychopharmacology Research Laboratories, Veterans Administration Hospital, Sepulveda, California; and the Department of Pharmacology, College of Medicine, University of Cali· fornia, Irvine, California (page 165)
Department of Biochemistry, Institute of Psychiatry, British Postgraduate Medical Federation, University of London, England (page 1)
Research Division of the Cleveland Clinic Foun· dation, Cleveland, Ohio; and the Department of Pharmacology, University of Göteborg, Sweden (page 251)
Psychopharmacology Research Laboratories ; Veterans Administration Hospital, Sepulveda, California; and the Department of Biological Chemistry, University of California, Los Angeles, California (page 165)
Department of Zoology, Michigan State University, East Lansing, Michigan (page 429)
Laboratory of Preclinical Pharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeth's Hospital, Washington, D.C. (page 45)
Department of Physiology, Australian National University, Canberra, Australia (page 115)
Section de Neuropharmacologie Biochimique du Laboratoire de Neurophysiologie Generale du College de France (page 91)
Department of Anatomy and Brain Research In· stitute, UCLA School of Medicine, Los Angeles, California (page 429)
Department of Pharmacology, Mount Sinai School of Medicine, N ew Y ork, N ew Y ork (page 221)
RoH Hilkanson
LesIie L. Iversen
Graham A. R. Johnston
Rohert Katzman
Erling Mellerup
K.'D.Neame
N. H. Neff
J. H. Quastel
Irvine H. Page
Lincoln T. Potter
OIe J. Rafaelsen
Max Reiss
Department of Pharmacology, University of Lund, Lund, Sweden (page 165)
Department of Pharmacology, University of Cambridge, Cambridge, England (page 197)
Department of Physiology, Australian National University, Canberra, Australia (page 115)
The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York (page 313)
Psychochemical Laboratory, University Clinic of Psychiatry, Rigshospitalet, Copenhagen, Den. mark (page 361)
Department of Physiology, University of Liver· pool, Liverpool, England (page 329)
Laboratory of Preclinical Pharmacology, Divi, sion of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D.e. (page 45)
Kinsmen Laboratories of Neurological Re· search, Faculty of Medicine, University of British Columbia, Vancouver, Re., Canada (page 285)
Research Division of the Cleveland Clinic Foundation, Cleveland, Ohio; and the Department of Pharmacology, University of Göteborg, Sweden (page 251)
Biophysics Department, University College, London, England (page 263)
Psychochemical Laboratory, University Clinic of Psychiatry, Rigshospitalet, Copenhagen, Denmark (page 361)
Neuroendocrine Research Unit, Willowbrook State School, Staten Island, New York (page 463)
Howard Sachs
George J. Siegel
Leonhard S. Wolfe
R. J. W urtman
G. Zetler
Roche Institute of Molecular Biology, Nutley, New Jersey (page 373)
Departments of Neurology and Physiology, Mount Sinai School of Medicine of The City University of New York, New York (page 13)
The Donner Laboratory of Experimental Neuro· chemistry, Montreal Neurological Institute and the Department of Neurology and Neurosur· gery, McGill University, Montreal, Canada (page 149)
Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts (page 451)
Department of Pharmacology, Medizinsehe Akademie Lübeck, Lübeck, Germany (page 135)
PREFACE
The explosive accumulation of new knowledge in the biological sciences in the last decades has advanced our understanding of the basic mechanisms that underlie most biological phenomena. These advances, however, have not been uniform but have varied considerably among the different biological problems. In some cases, e.g., biochemical genetics, radical advances have been made which have changed our ideas and our approaches. In other cases, even with work which has yielded much detailed new knowledge, our understanding of basic mechanisms remains very inadequate.
Among the lines of work that have not yet led to dramatic conceptual advances is the problem of control of biological activities. This problem is, of course, basic both to any full understanding of life as a whole, and to any real understanding of its most minute phenomena. Indeed, the myriad of biological activities that we can observe by direct or indirect means are all under the sway of most exquisitely precise mechanisms. Any malfunctioning of these mechanisms has serious consequences, not only for the particular function itself, but for all the related and interlinked activities.
It is quite possible that the failure to have made definitive progress towards the elucidation of the basic mechanisms of control may be a consequence of the very nature of the knowledge that we are seeking, in the sense that, to formulate in exact terms the uniquely precise mechanisms of control, it is necessary to know first much more than we know at present about the phenomena being controlled.
Under the circumstances, the editor setting out to gather the information available on control mechanisms has a very difficult job indeed. On the one hand he might bring together as much information as might be relevant to the question of control; on the other, he might limit himself to reviewing in depth mechanisms already known to be related to control. In the first case, the result might be a prolix and diffuse enumeration of tenuously related subjects with a loss of emphasis on the really significant points. In the second case he might very well overlook what may eventually prove to be crucial. In the present volume, Dr. Abel Lajtha has skillfully avoided these potential drawbacks and has put together a group of chapters which cover their subject thoroughly but concisely, and in which proper emphasis is not lost. He has done this by avoiding any overall hypo thesis and by staying within the limits of positive knowledge. He has divided this body of knowledge into fairly homogeneous subjects, which he has succeeded in having reviewed by
ix
x Preface
authors highly knowledgeable in their respective fields. Specifically, he has treated the transmitters and their metabolism, the enzymes presumably involved in transmission and other neural activities, the hormones related to contral, and, finally, some biological phenomena which are necessarily related to control.
The final result of his careful editing is to have made available under a single cover a wealth of information that would require considerable effort to gather from other sources. Thus it will be possible for the reader to obtain, rapidlyand economically, specific information both on the various problems reviewed and on their significance to the overall question ofbiological control of the nervous tissue.
J. Folch-Pi, M.D. August1969
CONTENTS
Chapter 1
Control of Carbohydrate Metabolism ........................ '. . . 1 by H. S. Bachelard
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 11. Electrical Activity and Ion Movements. . . . . . . . . . . . . . . . . . . . 3 111. Glucose Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 IV. Glycolysis............................................ 4
A. Glycogen Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 B. Glycolytic Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
V. Hormones and Drugs. . . . ... . . . . . . . . . . . . . . .. . . . . . . . .. . . . 8 VI. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 VII. Refurences .......................................... 9
Chapter 2
Nucleoside Triphosphate Phosphohydrolases . . . . . . . . . . . . . . . . . . . . . 13 by George J. Siegel and R. Wayne Albers
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 A. Classification........................................ 14 B. Nonfunctional and Pseudo-ATPases. . . . . . . . . . . . . . . . . . . . 14
II. ATPase Activities Related to Contractile Proteins .......... 14 A. Myosin............................................. 15 B. Actin.............................................. 18
III. ATPase Activity of Mitochondria ....................... 21 IV. ATPases Associated with Active Transport ............... 22
A. Na-K-ATPase....................................... 22 B. Correlation of the Properties of Na-K-ATPase with the
Requirements of the Sodium Pump. . . . . . . . . . . . . . . . . . 27 C. Metabolie Regulation and Cation Transport. . . . . . . . . . . . . 28 D. Ca-ATPase of Sarcoplasmic Reticulum ................. 29 E. Other A TPases Possibly Related to Transport. . . . . . . . . . . . 32
xi
xii Contents
V. GTPase Associated with Protein Synthesis . . . . . . . . . . . . . . . . . 33 VI. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Chapter 3
Estimation of Turnover Rates to Study the Metabolie Regulation of the Steady-State Level of Neuronal Monoamines .................... 45 by E. Costa and N. H. Neff
I. Introduction........................................... 45 11. Monoamine Turnover Models. . . . . . . . . . . . . . . . . . . . . . . . . . . 46
A. Conceptual Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 B. Morphological Considerations. . . . . . . . . . . . . . . . . . . . . . . . . 47 C. Biochemical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 D. Physiological Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . 52
III. Catecholamine Turnover . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 A. Synopsis of Catecholamine Biosynthesis. . . . . . . . . . . . . . . . . 53 B. Synopsis of Catecholamine Metabolism. . . . . . . . . . . . . . . . . 55
IV. Methods of Estimating Catecholamine Turnover. . . . . . . . . . . 56 A. Isotopic Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 B. Nonisotopic Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
V. Serotonin Turnover . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 A. Synopsis of Serotonin Biosynthesis . . . . . . . . . . . . . . . . . . . . . 67 B. Synopsis of Serotonin Metabolism ..................... 68
VI. Methods of Estimating Serotonin Turnover . . . . . . . . . . . . . . . 68 A. Isotopic Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 B. Nonisotopic Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
VII. Effect of Drugs on Monoamine Turnover . . . . . . . . . . . . . . . . 72 A. Catecholamines ..................................... 72 B. Serotonin........................................... 77
VIII. Conclusions ........................................ 78 IX. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Chapter 4
Storage and Release of Monoamines in the Central Nervous System 91 by Jacques Glowinski
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 A. Historical Background ............................... 91 B. Localization of Central Amine-Containing Neurons ...... 92 C. Definition of Storage and Release Processes ............. 93
11. Storage of Monoamines ................................ 94 A. The Intraneuronal Gross Distribution ofCatecholamines and
Serotonin. ....................................... 94
Contents xiii
B. Storage of Exogenous Monoamines in Central Aminergic Neurons.. . . ... . . . . . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . 95
C. The Subcellular Localization of Monoamines . . . . . . . . . . . . 97 D. Characteristics of Storage Vesicles of Monoaminergic
Neurons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 E. Different Forms of Storage. . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 F. Effects of Drugs on the Storage of Monoamines . . . . . . . . . . 101
III. Release of Central Monoamines . . . . . . . . . . . . . . . . . . . . . . . . . 104 A. Direct Evidence of Release. . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 B. Indirect Demonstration of Release. . . . . . . . . . . . . . . . . . . . . 106 C. Mechanisms of Release Processes ..... . . . . . . . . . . . . . . . . . 108
IV. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 V. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Chapter 5
Amino Acid Transmitters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 by David R. Curtis and Graham A. R. Johnston
I. Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .. .. . . . . . .. 115 II. Investigation of Amino Acid Transmitter Function. . . . . . . . . . . 115
A. Synthesis and Storage within the Presynaptic Neuron. . . . . . . 116 B. Release from Presynaptic Terminals. . . . . . . . . . . . . . . . . . . . . 117 C. Postsynaptic Action. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 D. Postsynaptic Antagonists ............................. 119 E. Inactivation and Removal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
III. y-Aminobutyric Acid and Related Amino Acids. . . . . . . . . . . 120 A. Invertebrate......................................... 120 B. Vertebrate.......................................... 122
IV. Glycine and Related Amino Acids. . . . . . . . . . . . . . . . . . . . . . . 124 V. L-Glutamate and Related Derivatives. . . . . . . . . . . . . . . . . . . . . 128
A. Invertebrate......................................... 128 B. Vertebrate .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
VI. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 VII. References .......................................... 131
Chapter 6
Biologically Active Peptides (Substance P). . . . . . . . . . . . . . . . . . . . . . . 135 by G. Zetler
I. Introduction........................................... 135 11. The Old Concept of Substance P . . . . . . . . . . . . . . . . . . . . . . . . . 136
A. Extraction, Estimation, Purification ...... . . . . . . . . . . . . . . 136
xiv Contents
B. Chemie al Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 C. Distribution ........................................ 139 D. Pharmacological Actions ............................. 140
111. Crude Substance P as a Mixture of Peptides. . . . . . . . . . . . . . . 141 A. Chromatographie Basis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 B. Biochemical and Pharmacological Characteristics ........ 141 C. Differences Between Brain Areas . . . . . . . . . . . . . . . . . . . . . . . 143
IV. Release of Peptides from Precursors or Structures. . . . . . . . . . 144 V. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 VI. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Chapter 7
Biologically Active Lipids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 by Leonhard S. Wolfe
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 11. Discovery, Chemistry and Metabolism of Prostaglandins . . . . 150 111. Distribution of Prostaglandins in Tissues . . . . . . . . . . . . . . . . . 155 IV. Brain Prostaglandins and the Effect of Prostaglandins on Brain 156 V. Release of Prostaglandins from Organs by Nerve Stimulation,
Venoms, and Other Treatments. . . . . . . . . . . . . . . . . . . . . . . . 157 A. Iris and Irins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 B. Stomaeh, Intestine, and Darmstoff . . . . . . . . . . . . . . . . . . . . . 158 C. Spleen, Adrenals, and Adipose Tissue. . . . . . . . . . . . . . . . . . . 160
VI. Other Pharmacologically Active Lipids. . . . . . . . . . . . . . . . . . . 160 VII. References .......................................... 161
Chapter 8
Histidine Decarboxylase and DOPA Decarboxylase. . ... ... ... . . . . 165 by Dorothea Aures, Rolf Häkanson, and William G. Clark
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 11. Amine Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 111. General Mechanism of Amino Acid Decarboxylation ...... 167 IV. Methods for the Assay of Amino Acid Decarboxylases ..... 170
A. Aromatic L-Amino Acid Decarboxylase . . . . . . . . . . . . . . . . . 170 B. L-Histidine Decarboxylase ............................ 171 C. Critical Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
V. General Properties of DOPA Decarboxylase and Histidine Decarboxylase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
VI. Methods for the Purification of DOPA Decarboxylase and HD Decarboxylase.................................. 175
A. L-Dopa Decarboxylase ............................... 175 B. L-Histidine Decarboxylase ............................ 176
Contents xv
VII. Kinetic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 VIII. Distribution and Properties of Histidine Decarboxylase and
DOPA Decarboxylase in Nervous Tissue. . . . . . . . . . . . . 178 A. L-Histidine Decarboxylase ............................ 178 B. Aromatic L-Amino Acid Decarboxylase . . . . . . . . . . . . . . . . . 178
IX. Inhibition of Decarboxylases ........................... 179 X. Actions and Side Actions of Antidecarboxylases In Vivo . . . . . 183 XI. Behavioral Significance of Amino Acid Decarboxylases . . . . . 185 XII. References .................. . . . . . . . . . . . . . . . . . . . . . . . . 187
Chapter 9
Metabolism of Catecholamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197 by Leslie L. Iverson
I. Distribution of Catecholamines . . . . . . . . . . . . . . . . . . . . . . . . . . . 197 11. Biosynthesis of Catecholamines . . . . . . . . . . . . . . . . . . . . . . . . . . 198
A. Overall Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 B. Properties ofIndividual Enzymes ...................... 199 C. Subcellular and Cellular Distribution of Biosynthetic En-
zymes........................................... 202 D. Regulation of Catecholamine Biosynthesis. . . . . . . . . . . . . . . 203 E. Inhibitors of Catecholamine Biosynthesis. . . . . . . . . . . . . . . . 205
III. The Catabolism of Catecholamines . . . . . . . . . . . . . . . . . . . . . . 206 A. Metabolie Pathways. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206 B. Individual Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208 C. Cellular and Subcellular Distribution of MAO and COMT 210 D. Inhibitors of MAO and CO MT . . . . . . . . . . . . . . . . . . . . . . . . 211 E. Role of MAO and COMT in Adrenergic Transmission... . 213
IV. Other Pathways of Catecholamine Metabolism. . . . . . . . . . . . 214 A. Alternative Biosynthetic Pathways ..................... 214 B. Oxidation ofCatecholamines to Adrenochromes and Melanin 214
V. Comparative Aspects of Catecholamine Metabolism. . . . . . . . 215 VI. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
Chapter JO
Histamine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221 by J ack Peter Green
I. Measurement of Histamine in Neural Tissues . . . . . . . . . . . . . . . 221 11. Concentration and Distribution of Histamine in Brain and
Associated Structures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 A. Concentration in Whole Brain . . . . . . . . . . . . . . . . . . . . . . . . . 223 B. Regional Distribution in Brain. . . . . . . . . . . . . . . . . . . . . . . . . 223 C. Subcellular Distribution in Brain. . . . . . . . . . . . . . . . . . . . . . . 227
xvi Contents
III. Concentration of Histamine in Peripheral Nervous System. . 228 IV. Mast Cells in Peripheral Nerve: a Source of Histamine ..... 228 V. The Source ofHistamine in the Nervous System: the Formation
of Histamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230 VI. Binding of Histamine by Neural Tissue . . . . . . . . . . . . . . . . . . . 230 VI I. Aspects ofthe Chemistry of Histamine Pertinent to its Binding
and Its Biological Activities . . . . . . . . . . . . . . . . . . . . . . . . . 231 VIII. Pathways for the Catabolism of Histamine. . . . . . . . . . . . . . 232 IX. Catabolism of Histamine by Neural Tissue. . . . . . . . . . . . . . . . 234 X. Catabolites of Histamine in Neural Tissue . . . . . . . . . . . . . . . . . 234 XI. Are the Catabolites of Histamine "Inactivation Products"? . 236 XII. Histamine and Neural Activity . . . . . . . . . . . . . . . . . . . . . . . . . 238
A. The Effect of Exogenous Histamine on Neural Tissues .... 238 B. Endogenous Histamine and the Nervous System ......... 239
XIII. Summary........................................... 243 XIV. References.......................................... 244
Chapter 11
Serotonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251 by Irvine H. Page and Arvid Carlsson
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251 11. Distribution........................................... 251 III. Synthesis and Degradation of Serotonin. . . . . . . . . . . . . . . . . . 252
A. 5-Hydroxylation of Tryptophan in Brain . . . . . . . . . . . . . . . . 252 B. Breakdown of Serotonin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 C. Methylation of Serotonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 D. Tryptophol ......................................... 254
IV. Other Psychotropic Drugs and Serotonin. . . . . . . . . . . . . . . . . 254 A. Imipramine......................................... 254 B. Reserpine and Serotonin- Kinetics. . . . . . . . . . . . . . . . . . . . . 255
V. Serotonin as a Neural Transmitter. . . . . . . . . . . . . . . . . . . . . . . . 257 VI. Lysergic Acid Diethylamide (LSD) ...................... 258 VII. Serotonin and Temperature Control. . . . . . . . . . . . . . . . . . . . . 259 VIII. Serotonin and Mental Disease . . . . . . . . . . . . . . . . . . . . . . . . . 259 IX. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Chapter 12
Acetylcholine, Choline Acetyltransferase, and Acetylcholinesterase 263 by Lincoln T. Potter
I. Acetylcholine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Contents xvii
A. Acetylcholine as a Chemical Transmitter. . . . . . . . . . . . . . . . 263 B. Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
11. Choline Acetyltransferase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268 A. Biology ............................................ 268 B. Enzymology ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
III. Acetylcholinesterase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 A. Biology ............................................ 273
IV. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Chapter 13
Amine Oxidases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 by J. H. Quastel
I. Historical ............................................. 285 II. Detection and Estimation of Amine Oxidase. . . . . . . . . . . . . . . . 288
A. Methods in Vitro .................................... 288 B. Methods in Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
III. Distribution of Amine Oxidase. . . . . . . . . . . . . . . . . . . . . . . . . . 290 A. Cellular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 B. Subcellular ......................................... 290 C. In the Developing Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
IV. Effects of Increased Oxygen Tension. . . . . . . . . . . . . . . . . . . . . 292 V. Substrates of MAO .................................... 292 VI. Food, and Substrates of MAO . . . . . . . . . . . . . . . . . . . . . . . . . . 294 VII. Inhibitors of MAO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
A. Reversible Inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296 B. Irreversible Hydrazine Inhibitors. . . . . . . . . . . . . . . . . . . . . . . 296 C. Nonhydrazine Inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 D. Other MAO Inhibitors ............................... 298
VIII. Riboflavin and MAO ................................ 299 IX. Hormones and MAO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 X. Metabolic Functions of MAO ..... . . . . . . . . . . . . . . . . . . . . . . 299 XI. Isozymes of MAO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 XII. Dopamine-ß-Oxidase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 XIII. Other Amine Oxidases ............................... 301
A. Diamine Oxidases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 B. Spermine Oxidase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 C. Benzylamine Oxidase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 D. Cofactors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
XIV. Some Effects of MAO Inhibitors. . . . . . . . . . . . . . . . . . . . . . . 303 V. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
xviii Contents
Chapter 14
Ion Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 by Robert Katzman
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 11. Blood-Brain Barrier-Restriction of Ion Exchange. . . . . . . . . 314 III. Equations for Calculation oflon Flux. . . . . . . . . . . . . . . . . . . . 315 IV. Maintenance of Constant Ionic Environment. . . . . . . . . . . . . . 319 V. Mediated Flux. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 VII. Carrier-Mediated and Active Clearance of Anions: Bromide
and Iodide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 VII. Cation Effiux . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 VIII. Relationship ofCSF and the Extracellular Fluid ofthe Brain 324 IX. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Chapter 15
Transport ofMonosaccharides, Amines, and Certain Other Metabolites 329 by K. D. Neame
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329 11. Monosaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 111. Amines.............................................. 336
A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 B. Catecholamines ..................................... 337 C. 5-Hydroxytryptamine ................................ 342 D. Histamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345 E. Conclusions......................................... 347
IV. Miscellaneous Compounds . . . . . . . . . . . . .. . . . . . . . . . . . . . . . 349 A. Quaternary Ammonium Compounds . . . . . . . . . . . . . . . . . . . 349 B. Urea............................................... 350 C. Cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 D. Other Metabolites. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
V. Conclusions........................................... 351 VI. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
Chapter 16
Insulin Action. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 by OIe J. Rafaelsen and Erling Mellerup
I. General Action of Insulin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Contents xix
11. In Vitro Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 III. Animal Experiments in Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
A. Direct Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 B. Indirect Action. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
IV. Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367 V. Conclusion..................................... . . . . . . . 369 VI. References ........................................... 370
Chapter 17
Neurosecretion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 by Howard Sachs
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 11. Characteristics of the Neurosecretory Cell . . . . . . . . . . . . . . . . . 373
A. Classical Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 B. Inadequacies ofthe Classical Formulation ofNeurosecretion 375
III. Significance of the Neurosecretory Cell . . . . . . . . . . . . . . . . . . . 377 IV. Distribution and Functions of Neurosecretory Cells . . . . . . . . 378 V. The Hypothalamo-Neurohypophyseal Complex, a Model
System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380 A. Morphological Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381 B. Hormonal Activities, Chemistry, Functions, and Evolu-
tionary Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382 C. The Neurosecretory Process . . . . . . . . . . . . . . . . . . . . . . . . . . . 385 D. Separate Neurosecretory Granules for Oxytocin and Vaso-
pressin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392 VI. Neurophysin, Chemistry and Functions .................. 392 VII. Biosynthetic Pathways ......... . . . . . . . . . . . . . . . . . . . . . . . 395
A. Anatomical and Intracellular Loci of Hormone Biosynthesis 396 B. Enzymatic Pathways of Hormone Biosynthesis . . . . . . . . . . . 400 C. Synthesis of Oxytocin and Vasopressin in Separate Neurons 402 D. Simultaneous Biosynthesis of Hormones and Their Carrier
Pro teins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402 E. The Rates of Hormone Biosynthesis . . . . . . . . . . . . . . . . . . . . 402
VIII. Secretory Mechanisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406 A. Nerve Excitation and Hormone Release. . . . . . . . . . . . . . . . . 406 B. Excitation-Secretion Coupling. . . . . . . . . . . . . . . . . . . . . . . . . 407 C. Secretion of the Total Neurosecretory Substance . . . . . . . . . 411
IX. The Neurosecretory Neuron and the Interstitial Neuroglial Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
X. Summary ................. , . . . . . . . . . . . . . . . . . . . . . . . . . . . 417 XI. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420
xx Contents
Chapter 18
Action of Gonadal Hormones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429 by Roger A. Gorski and Lynwood G. Clemens
I. Introduction ................................... : . . . . . . . 429 II. Functional Interactions between Brain and Gonads. . . . . . . . . . 429
A. The Adult Animal .......... . . . . . . . . . . . . . . . . . . . . . . . . . 430 B. Inftuence of Animal Development on Hormone Action. . . . 433
III. Gonadal Hormones and Neurobiochemical Processes ...... 436 A. The Initial Association ............................... 436 B. Morphological Processes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437 C. Metabolie Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438 D. Molecular Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441
IV. Electrical Correlates of Gonadal Hormone Action . . . . . . . . . 442 V. The Temporal Pattern of Hormone Action ................ 443
A. Regulation of Hypophyseal Activity . . . . . . . . . . . . . . . . . . . . 443 B. Regulation of Sexual Behavior. . . . . . . . . . . . . . . . . . . . . . . . . 445
VI. Conclusion...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445 VII. References .......................................... 446
Chapter 19
Pineal Hormones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451 by R. J. Wurtman
I. Introduction........................................... 451 11. The Evolution of the Mammalian Pineal Gland . . . . . . . . . . . . 452 III. Mediation of the Photic Control of the Mammalian Pineal by
Sympathetic Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452 IV. Metabolism of Serotonin in the Mammalian Pineal ........ 453 V. Synthesis and Fate of Melatonin . . . . . . . . . . . . . . . . . . . . . . . . . 455 VI. Pineal Biochemical Rhythms. . . . . . . . . . . . . . . . . . . . . . . . . . . . 456 VII. Summary ........................................... 459 VIII. References.......................................... 459
Chapter 20
The Hypothalamo-Hypophyseal Complex . . . . . . . . . . . . . . . . . . . . . . . 463 by Max Reiss
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463 II. The Significance of the Hypothalamo-Hypophyseal Complex
in the Homeostasis of the Body . . . . . . . . . . . . . . . . . . . . . . . 463
Contents xxi
Ill. Biological Criteria and Proof for the Production of Release Factors in the Hypothalamus. . . . . . . . . . . . . . . . . . . . . . . . 465
A. Interrelation between the Hypothalamus and Pituitary Pos-terior Lobe ...................................... 465
B. Interrelation between the Hypothalamus and Pituitary An-terior Lobe ............... . . . . . . . . . . . . . . . . . . . . . . . 469
C. Pituitary Anterior Lobe Hormones. . . . . . . . . . . . . . . . . . . . . 476 D. Pars Intermedia Melanocyte Stimulation and the Hypo-
thalamus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 IV. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 V. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493
Subject Index .............................................. 507
top related