Table Of ContentCholinergic
Mechanisms and
Psychopharmacology
ADVANCES IN BEHAVIORAL BIOLOGY
Editorial Board:
Jan Bures Institute of Physiology, Prague, Czechoslovakia
Irwin Kopin National Institute of Mental Health, Bethesda, Maryland
Bruce McEwen Rockefeller University, New York, New York
James McGaugh University of California, Irvine, California
Karl Pribram Stanford University School of Medicine, Stanford, California
Jay Rosenblatt Rutgers University, Newark, New Jersey
Lawrence Weiskrantz University of Oxford, Oxford, England
Recent Volumes in this Series
Volume 12. THE NEUROPSYCHOLOGY OF AGGRESSION
Edited by Richard E. Whalen. 1974
Voilime 13. ANEURAL ORGANISMS IN NEUROBIOLOGY
Edited by Edward M. Eisenstein. 1975
Volume 14. NUTRITION AND MENTAL FUNCTIONS
Edited by George Serban • 1975
Volume 15. SENSORY PHYSIOLOGY AND BEHAVIOR
Edited by Rachel Galun, Peter Hillman, Itzhak Parnas,
and Robert Werman. 1975
Volume 16. NEUROBIOLOGY OF AGING
Edited by J. M. Ordy and K. R. Brizzee. 1975
Volume 17. ENVIRONMENTS AS THERAPY FOR BRAIN DYSFUNCTION
Edited by Roger N. Walsh and William T. Greenough. 1976
Volume 18. NEURAL CONTROL OF LOCOMOTION
Edited by Richard M. Herman, Sten Grillner, Paul S. G. Stein,
and Douglas G. Stuart. 1976
Volume 19. THE BIOLOGY OF THE SCHIZOPHRENIC PROCESS
Edited by Stewart Wolf and Beatrice Bishop Berle • 1976
Volume 20 • THE SEPTAL NUCLEI
Edited by Jon F. DeFrance. 1976
Volume 21 • COCAINE AND OTHER STIMULANTS
Edited by Everett H. Ellinwood, Jr. and M. Marlyne Kilbey • 1977
Volume 22. DISCRIMINATIVE STIMULUS PROPERTIES OF DRUGS
Edited by Harbans Lal • 1977
Volume 23. THE AGING BRAIN AND SENILE DEMENTIA
Edited by Kalidas Nandy and Ira Sherwin. 1977
Volume 24. CHOLINERGIC MECHANISMS AND PSYCHOPHARMACOLOGY
Edited by Donald J. Jenden • 1977
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Cholinergic
Mechanisms and
Psychopharmacology
Edited by
Donald J. Jenden
t:h~OI
University of California of Medicine
Los Angeles, California
Plenum Press · New York and London
,
Library of Congress Cataloging in Publication Data
Symposium on Cholinergic Mechanisms and Psychopharmacology, La Jolla, Calif.,
1977.
Cholinergic mechanisms and psychopharmacology.
(Advances in behavioral biology; v. 24)
Includes index.
1. Psychopharmacology-Congresses. 2. Acetylcholine-Congresses. 3. Cholinergic
receptors-Congresses. I. Jenden, Donald J. II. United States. Psychopharmacology
Research Branch. Pharmacology Section. III. International Union of Pharmacology.
IV. Title.
RM315.S941977 615'.78 77·14956
ISBN· 13: 978·1·4684·3098·1 e·ISBN· 13: 978·1-4684·3096·7
001: 10.1007/978·1-4684·3096·7
Proceedings of a Symposium on Cholinergic Mechanisms and Psychopharmacology
held in La Jolla, California, March 28-31, 1977
© 1978 Plenum Press, New York
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
Softcover reprint of the hardcover 1s t edition 1978
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
SYMPOSIUM ON
Cholinergic Mechanisms and Psychopharmacology
La Jolla, California, March 28-31, 1977
ORGANIZING COMMITTEE
Bo Holmstedt
Department of Toxicology
Swedish Medical Research Council
KBrolinska Institute
Stockholm, Sweden
George B. Koelle
Department of Pharmacology
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania
Earl Usdin
Pharmacology Section, Psychopharmacology Research Branch
National Institute of Mental Health
Rockville, Maryland
Peter G. Waser
Institute of Pharmacology
University of Zurich
Zurich, Switzerland
Victor P. Whittaker
Max-Planck Institute of Biochemical Research
Division of Neurochemistry
Gottingen, West Germany
Donald J. Jenden, Chairman
Department of Pharmacology
UCLA School of Medicine
Los Angeles, California
SPONSORED BY
Pharmacology Section, Psychopharmacology Research Branch, National
Institute of Mental Health (MH-29559)
International Union of Pharmacology (lUPHAR)
ACKNOWLEDGMENT IS MADE FOR GENEROUS
SUPPORT BY
Abbott Laboratories
Ayerst Laboratories
Hoffman-La Roche, Inc.
Merck Sharp & Dohme
Merrell-National Laboratories
Parke-Davis
Pennwalt Corporation
Riker Laboratories
Wyeth Laboratories
Pharmacology Section,
Psychopharmacology Research Branch,
National Institute of Mental Health (MH-29559)
PREFACE
This volume represents a collection of papers which were contributed
by participants at a Symposium for Cholinergic Mechanisms and Psycho
pharmacology, held in La Jolla, California on March 28-30, 1977. The
topics were chosen to emphasize areas in which there has been substantial
progress in the past 2-3 years and fall into seven major groups dealingwith:
cholinergiC receptors; chemistry, histochemistry and enzymology; cyclic
nucleotides and cholinergiC mechanisms; storage, compartmentation and
release of acetylcholine; regulatory mechanisms in acetylcholine metab
olism; modulation of acetylcholine metabolism; and behavioral and clin
ical manifestations of cholinergiC function and dysfunction. Each group
contains one or more reviews and a number of shorter contributions de
scribing current work.
This symposium was the third in a series of which the first two were
held in Skokloster, Sweden in 1970 and Boldern, Switzerland in 1974. The
Proceedings of the meetings indicate a rapid development of knowledge of
cholinergiC mechanisms which for many years lagged behind that of other
neurotransmitters and neuroregulators. The inclusion of a large section
in the present volume dealing with clinical manifestations of cholinergiC
dysfunction reflects one of the most important trends in current research
on cholinergiC mechanisms, namely the close inter-relationship and mutual
support of basic science and clinical investigation. I hope that this volume
will be of value to all those whose work relates to cholinergiC function, at
both basic and clinicalleve18, and will continue to stimulate the vigorous
exchange of ideas which was such a prominent feature of the Symposium.
I would like to thank all my friends and colleagues whose help contrib
uted to the success of the SympOSium, and the organizations who helped to
defray its expenses, particularly the Pharmacology Section, Psychophar
macology Research Branch of the National Institute of Mental Health, which
provided most of its financial support. Thanks are also due to Kevin
Haynes for his careful preparation of the author index.
Special thanks must go to Mrs. Flo Comes for her skillful organization
and dedication to our common purpose, from the initial arrangements for
the conference to editing of the manuscripts and preparation of the final
copy.
Donald J. J enden
Los Angeles, Cali fornia
August, 1977
vii
CONTENTS
CHOLINERGIC RECEPTORS
THE BINDING OF ACETYLCHOLINE TO ITS NICOTINIC
RECEPTOR
R. D. O'Brien & R. E. Gibson 1
CORRELATION BETWEEN THE BINDING PROPERTIES AND
PHARMACOLOGICAL RESPONSES ON MUSCARINIC
RECEPTORS
N. J. M. Birdsall, A. S. V. Burgen & E. C. Hulme 25
BIOCHEMICAL CHARACTERIZATION OF MUSCARINIC
CHOLINERGIC RECEPTORS IN HUNTINGTON'S DISEASE
H.1. Yamamura, G. J. Wastek, p. C. Johnson &
L. Z. Stern 35
CHARACTERIZATION OF PRESYNAPTIC MUSCARINIC
RECEPTORS IN CENTRAL CHOLINERGIC NEURONS
J. C. Szerb 49
ARE THERE TWO FORMS OF NICOTINIC ACETYLCHOLINE
RECEPTORS
T. Mittag, T. Massa & S. Gross 61
IMMUNOFLUORESCENCE ANALYSIS OF SURFACE ACETYL
CHOLINE RECEPTORS ON MUSCLE: MODULATION BY
AUTO-ANTIBODIES
V.A. Lennon 77
CHEMISTRY, HISTOCHEMISTRY & ENZYMOLOGY
RECENT ADVANCES IN HISTOCHEMICAL TECHNIQUES FOR
THE STUDY OF CENTRAL CHOLINERGIC MECHANISMS
L. L. Butcher 93
HISTOCHEMICAL AND PHARMACOLOGICAL EVIDENCE OF
THE FUNCTION OF BUTYRYLCHOLINESTERASE
G. B. Koelle, W. A. Koelle, E. G. Smyrl, R. Davis
& A. F. Nagle 125
ESTIMATION OF ACETYLCHOLINE AND THE DYNAMICS
OF ITS METABOLISM
D. J. Jenden 139
ix
x CONTENTS
RADIOIMMUNOASSAY FOR ACETYLCHOLINE
S. Spector, A. M. Felix & J. p. M. Finberg 163
MICROWAVE FIXATION FOR THE STUDY OF ACETYL
CHOLINE METABOLISM
W.B. Stavinoha, J. Frazer & A. T. Modak 169
ACETYLCHOLINE AND CHOLINE IN HUMAN PLASMA AND
RED BLOOD CELLS: A GAS CHROMATOGRAPHIC MASS
SPECTROMETRIC EVALUATION
I. Hanin, U. Kopp, N. R. Zahniser, T.-M. Shih,
D. G. Spiker, J. R. Merikangas, D. J. Kupfer &
F. G. Foster 181
STUDIES ON THE MECHANISM OF ACTION OF CHOLINE
ACETYL TRANSFERASE
H. G. lVIautner & S. F. Currier 197
ACTIVATION OF CHOLINE ACETYLTRANSFERASE BY
CHLORIDE: A POSSIBLE REGULATOR MECHANISM
J. Rossier & p. Benda 207
COMPARATIVE IMMUNOCHEMISTRY OF MAMMALIAN
BRAIN AND EEL ELECTRIC TISSUE ACETYL
CHOLINESTERASES
A. J. Trevor & A. J. Greenberg 223
CONSTITUENTS OF ACETYLCHOLINESTERASE
G. Werner, W. Wojnarowski, W. H. Hopff &
p. G. Waser 231
STRUCTURE OF ACETYLCHOLINESTERASE: ITS
RELATIONSHIP TO THE POSTSYNAPTIC MEMBRANE
p. Taylor, J. Lwebuga-Mukasa, S. Lappi &
H.A. Berman 239
CYCLIC NUCLEOTIDES & CHOLINERGIC MECHANISMS
IF CYCLIC GMP IS A NEURONAL SECOND MESSENGER
WHAT IS THE MESSAGE
C. D. Woody 253
ACETYLCHOLINE AND CYCLIC GMP
K. Krnjevic 261
CONTENTS xi
CONTROL OF NUCLEAR FUNCTION IN CHROMAFFIN
CELLS BY PERSISTENT ACTIVATION OF NICOTINIC
RECEPTORS
E. Costa, D. M. Chuang, A. Guidotti &
R. Hollenbeck 267
MUSCARINIC STIMULATION AND cG MP SYNTHESIS
IN THE NERVOUS SYSTEM
T. Bartfai, R. E. Study & p. Greengard 285
STORAGE, COMPARTMENTATION & RELEASE OF ACETYLCHOLINE
THE PRESENT STATUS OF THE VESICLE HYPOTHESIS
F. C. MacIntosh 297
THE ELECTROMOTOR SYSTEM OF TORPEDO AS A
MODEL CHOLINERGIC SYSTEM
V. p. Whittaker 323
THE ENDOCYTOTIC ROLE OF VESICLES AT THE
CHOLINERGIC SYNAPSE
p. G. Waser & W. Naef 347
NERVE TERMINAL SACS FROM TORPEDO ELECTRIC
ORGAN: A NEW PREPARATION FOR THE STUDY OF PRE
SYNAPTIC CHOLINERGIC MECHANISMS AT THE
MOLECULAR LEVEL
M. J. Dowdall 359
ACETYLCHOLINE COMPARTMENTS IN FROG MUSCLE
R. Miledi, p. C. Molenaar & R. L. Polak 377
ACETYLCHOLINE MEDIA TED AXON-SCHW ANN CELL
RELATIONSHIPS IN THE SQUID NERVE FIBER
J. Villegas 387
MUSCARINIC MODULATION OF ACETYLCHOLINE RELEASE
FROM THE MYENTERIC PLEXUS OF THE GUINEA PIG
INTESTINE
H. Kilbinger 401
REGULATORY MECHANISMS IN ACETYLCHOLINE METABOLISM
SOURCE OF THE ACETYL GROUP IN ACETYLCHOLINE
J. H. Quastel 411
THE SOURCE OF CHOLINE FOR ACETYLCHOLINE SYNTHESIS
G. B. Ansell & S. Spanner 431
