Table Of ContentPROGRESS IN BRAIN RESEARCH
VOLUME 98
CHOLINERGIC FUNCTION AND
DYSFUNCTION
EDITED BY
A. CLAUD10 CUELLO
Department of Pharmacology and Therupeutics,
McGill University. Montreal, Quebec, Cunadu
ELSEVIER
AMSTERDAM - LONDON -NEW YORK -TOKYO
1993
Elsevier Science Publishers B.V.
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Cholinergic function and dysfunction / edited by A. Claudlo Cuello.
p. cm. -- (Progress in brain research ; v. 98)
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ISBN 0-444-89717-8 (alk. paper). -- ISBN 0-444-80104-9 (series :
alk. paper)
1. Cholinerglc mechanisms--Congresses. 2. Cholinesterases-
-metabolism--congresses. I. Cuello, A. C. (A. Claudio)
11. Series.
[DNLM 1. Central Nervous System--physiology--congresses.
2. Receptors. Cholinergic--physiology--congresses. 3. Cholinergic
Fibers--physiology--congresses. W1 PR667J v.98 1993 / WL 300 C547
19931
QP376.P7 vol. 98
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V
List of Contributors
M. Amador, Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
R. Amstutz, Preclinical Research, Sandoz Pharma Ltd., CH 4002 Basel, Switzerland
S.-M. Aquilonius, Department of Neurology, University Hospital, S-751 85, Uppsala, Sweden
D.M. Araujo, Douglas Hospital Research Centre and Department of Psychiatry, Faculty of Medicine, McGill
University, Montreal, QuBbec, Canada H4H 1R3
I. Aubert, Douglas Hospital Research Centre and Department of Psychiatry, and Department of Neurology and
Neurosurgery, Faculty of Medicine, McGill University, Montreal, Qutbec, Canada H4H 1R3
M. Bachoo, Department of Physiology, McGill University, Canada
B.A. Bahr, Department of Chemistry and the Neuroscience Research Institute, University of California, Santa
Barbara, CA 93106, USA
R. Ben Aziz-Aloya, Department of Biological Chemistry, The Life Sciences Institute, The Hebrew University of
Jerusalem, Jerusalem, 91 904, Israel
M. Benzi, Laboratory of Cholinergic Neuropharmacology, Istituto di Ricerche Farmacologiche "Mario Negri",
Milan, Italy
R. Bertorelli, Laboratory of Cholinergic Neuropharmacology, Istituto di Ricerche Farmacologiche "Mario Negri",
Milan, Italy
H. Boddeke, Preclinical Research, Sandoz Pharma Ltd., CH 4002 Basel, Switzerland
S. Bon, Laboratoire de Neurobiologie, CNRS URA 295, Ecole Normale Sup6rieure. 46 rue d'Ulm, 75005 Paris,
France
M.R. Brann, Molecular Neuropharmacology Section, Department of Psychiatry, University of Vermont,
Burlington, VT 05405, USA
D.A. Brown, Department of Pharmacology, University College London, Gower Street, London WClE 6BT, UK
A.S.V. Burgen, Department of Pharmacology, Cambridge University, Cambridge, UK
M.A. Burke-Watson, Department of Anatomy and Cell Biology, University of Illinois School of Medicine,
Chicago, IL 60612, USA
L.L. Butcher, Laboratory of Chemical Neuroanatomy, Department of Psychology, University of California, Los
Angeles, CA 90024-1563, USA
M.J. Callahan, Department of Pharmacology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann
Arbor, MI 48 105, USA
J.M. Calvo, Laboratory of Neurophysiology, Department of Psychiatry, Harvard Medical School, 74 Fenwood
Road, Boston, MA 021 15, USA
M.P. Caulfield. Department of Pharmacology, University College London, Gower Street, London WCI E 6BT, UK
P.B.S. Clarke, Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street,
Montreal, Canada H3G 1Y6
E.D. Clarkson, Department of Chemistry and the Neuroscience. Research Institute, University of California. Santa
Barbara, CA 93106, USA
R.C. Clatterbuck, Department of Neuroscience. and Neuropathology Laboratory, The Johns Hopkins University
School of Medicine, Baltimore, Maryland, USA
A.C. Cuello, McGill University, 3655 Drummond Street, Room 1325, Montreal, Quebec, Canada H3G 1Y6
B. Collier, Department of Pharmacology and Therapeutics, McGill University, Canada
S. Consolo. Laboratory of Cholinergic Neuropharmacology. Istituto di Ricerche Farmacologiche "Mario Negri",
Milan, Italy
W.E. Cullinan, Mental Health Research Institute, University of Michigan, Ann Arbor, MI, USA
J.A. Dani, Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
S. Datta, Laboratory of Neurophysiology, Department of Psychiatry, Harvard Medical School, 74 Fenwood Road,
Boston, MA 021 15, USA
R. Davis, Department of Pharmacology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor,
MI 48 105, USA
J.F. Dixon, Department of Pharmacology, University of Wisconsin Medical School, Madison, WI 53706, USA
vi
V. Doleial. Institute of Physiology, Czech Academy of Sciences, 14220 Prague, Czech Republic
D.T. Dudley, Department of Pharmacology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann
Arbor, MI 48105, USA
Y. Dunant, DCpartement de Phnrmacologie, Centre mddical universitaire, CH-1211 Geneva-4, Switzerland
S.B. Dunnett. Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge
CB2 3EB, UK
J. Ellis, Molecular Neuropharmacology Section, Department of Psychiatry, University of Vermont, Burlington. VT
05405, USA
A. Enz, Preclinical Research, Sandoz Pharma Ltd., CH 4002 Basel. Switzerland
H.C. Fibiger, Division of Neurological Sciences, University of British Columbia, 2255 Wesbrook Mall,
Vancouver, B.C., Canada V6T 123
F.H. Gage, Department of Neurosciences, UCSD, La Jolla, CA 92092-0627, USA
P. Gaudreau, Laboratory of Neuroendocrinology, Notre-Dame Hospital and Department of Medicine, University of
Montreal, Montreal, Quebec, Canada H3C 3T8
L. Gauthier. McGill Centre for Studies in Aging and School of Physical and Occupational Therapy, McCill
University, Montreal, Quebec, Canada
S. Gauthier. McGill Centre for Studies in Aging and School of Physical and Occupational Therapy, McGill
University, Montreal, Quebec, Canada
E. Giacobini. Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield, IL
62794-9230. USA
J.C. Gillin, Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0603 and San Diego
Veterans Affairs Medical Center, San Diego. CA, USA
P. Girotti, Laboratory of Cholinergic Neuropharmacology, lstituto di Ricerche Farmacologiche "Mario Negri",
Milan, Italy
G. Gmelin, Preclinical Research, Sandoz Pharma Ltd.. CH 4002 Basel, Switzerland
E. Gruen, Mental Retardation Research Center, Departments of Anatomy and Psychiatry, UCLA Center for Health
Sciences, Los Angeles, CA 90024, USA
1. Hanin, Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Stritch School
of Medicine, 2160 South First Avenue, Maywood, IL 60153. USA
F. Hefti, Division of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los
Angeles. CA 90089, USA
E. Heilbronn, Department of Neurochemistry and Neurotoxicology. Stockholm University, S-106 91 Stockholm,
Sweden
A. Hersi, Douglas Hospital Research Centre and Department of Psychiatry, Department of Neurology and
Neurosurgery, Faculty of Medicine, McGill University, Montreal, QuCbec, Canada H4H 1R 3, and Laboratory
of Neuroendocrinology. Notre-Dame Hospital and Department of Medicine, University of Montreal, Montreal.
Quebec, Canada H3C 3T8
B.W. Hicks, Department of Chemistry and the Neuroscience Research Institute. University of California, Santa
Barbara, CA 93106, USA
H. Higashida. Department of Biophysics, Kanazawa University School of Medicine, Takaramachi 13-1. Kanazawa
920, Japan
D. Hill-Eubanks, Molecular Neuropharmacology Section, Department of Psychiatry, University of Vermont,
Burlington, VT 05405, USA
J.A. Hobson, Laboratory of Neurophysiology, Department of Psychiatry, Harvard Medical School, 74 Fenwood
Road. Boston, MA 021 15, USA
L.E. Hokin, Department of Pharmacology, University of Wisconsin Medical School, Madison, WI 53706, USA
T. lijima, Electrotechnical Laboratory, Molecular and Cellular Neuroscience Division, Tsukuba, Ibaraki 305, Japan
K. Ikeda, Division of Neurosciences, Beckman Research Institute of the City of Hope, 1450 E. Duarte Road.
Duarte, CA 91010, USA
D.K. Ingram, Molecular Physiology and Genetics Section, Gerontology Research Center, National Institute of
Aging, Baltimore, MD, USA
M. Israel, Dkpartement de Neurochimie, Laboratoire de Neurobiologie cellulaire et molkculaire. C.N.R.S., F-91190
Gif-sur-Yvette, France
L.L. Iversen, Neuroscience Research Centre, Merck Sharp 13 Dohme Research Laboratories, PO Box 1675,
Harlow, Essex CM20 2PT, UK
J. Jaen, Department of Chemistry, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road. Ann Arbor, MI
48105, USA
R. Jahn, Department of Pharmacology and Howard Hughes Medical Institute, Yale University, New Haven, CT
06536, USA
vii
D.J. Jenden, Department of Pharmacology, UCLA School of Medicine, Los Angeles, CA 90024, USA
B.E. Jones, Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, 380 1
University Street, Montreal, Quebec, Canada H3A 2B4
S.V.P. Jones, Molecular Neuropharmacology Section, Department of Psychiatry, University of Vermont,
Burlington, VT 05405, USA
R.S. Jope, Department of Psychiatry and Behavioral Neurology, University of Alabama at Birmingham,
Birmingham, AL 35294-0017, USA
H. Jeirgensen, Molecular Neuropharmacology Section, Department of Psychiatry, University of Vermont,
Burlington, VT 05405, USA
J.A. Joseph, Molecular Physiology and Genetics Section, Gerontology Research Center, National Institute of
Aging, Baltimore, MD, USA
A.G. Karczmar, Department of Pharmacology, Loyola University Medical Center, Maywood, IL and Research
Services, Hines VA Hospital, Hines. IL, USA
T. Kitamoto, Division of Neurosciences, Beckman Research Institute of the City of Hope, 1450 E. Duarte Road,
Duarte, CA 91010, USA
J. Klein, Department of Pharmacology, University of Mainz, W-6500 Mainz, Germany
B. Knusel, Division of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los
Angeles, CA 90089, USA
V.E. Koliatsos, Departments of Pathology and Neurology, and Neuroscience, and Neuropathology Laboratory, The
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
A. Ktippen, Department of Pharmacology. University of Mainz. W-6500 Mainz, Germany
J. Kordower, Department of Neurological Sciences and Rush Alzheimer’s Center. Rush PresbyteridSt. Lukes
Medical Center, Chicago, IL 60612, USA
K. Krnjevi6, Anaesthesia Research Department, Room 1208, Mclntyre Medical Sciences Building. McCill
University, Montdal, QuCbec, Canada
Y. Kudo, Department of Neuroscience, Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194, Japan
H. Ladinsky, Department of Biochemistry and Molecular Pharmacology, Boehringer lngelheim Italia, Milan, Italy
P.A. Lapchak, Division of Neurogerontology, Andrus Gerontology Center, University of Southem California, Los
Angeles, CA 90089, USA
D. Lauffer, Department of Chemistry, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor, MI
48105, USA
W. Lipinski, Department of Pharmacology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann
Arbor, MI 48105, USA
K. Laffelholz, Department of Pharmacology, University of Mainz, W-6500 Mainz, Germany
C.A. Lucidi-Phillipi, Department of Neurosciences, UCSD, La Jolla, CA 92092-0627, USA
C. Luetje, Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
V.N. Luine, Department of Psychology, Hunter College of the City University of New York, New York, NY. USA
J. Malanowski, Preclinical Research, Sandoz Pharma Ltd., CH 4002 Basel, Switzerland
J. Massoulit, Laboratoire de Neurobiologie, CNRS URA 295, &ole Normale Suphieure, 46 rue d’Ulm, 75005
Paris, France
D.A. McCormick, Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven,
CT 06510, USA
M. McKinney, Department of Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL
32224, USA
G. Mengod. Centro Investigacih y Desanollo, Consejo Superior de Investigaciones Cientificas, Jordi Girona,
18-26,08034 Barcelona, Spain
R.F. Mervis, Neurometrix Imaging Research, Inc., Columbus, OH, USA
H.C. Moises, Department of Physiology, University of Michigan, Ann Arbor, MI USA
E.J. Mufson, Department of Neurological Sciences and Rush Alzheimer’s Center, Rush PresbyteridSt. Lukes
Medical Center, Chicago, IL 60612, USA
T. Nabeshima. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of
Medicine, Nagoya 466, Japan
K. Nakamura, Department of Neuroscience, Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194,
Japan
K. Noguchi. Department of Neuroscience, Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194, Japan
K. Noremberg. Department of Chemistry and the Neuroscience Research Institute, University of California, Santa
Barbara, CA 93106, USA
A. Ogura, Department of Neuroscience, Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194, Japan
viii
J.D. Oh, Laboratory of Chemical Neuroanatomy, Department of Fsychology, University of California, Los Angeles,
CA 90024-1563, USA
J.M. Palacios, Centro Investigaci6n y Desarrollo, Consejo Superior de Investigaciones Cientificas, Jordi Girona,
18-26, 08034 Barcelona. Spain and Research Institute, Laboratorios Almirall, Cardener. 68-74, 08024
Barcelona, Spain
S.M. Parsons, Department of Chemistry and the Neuroscience Research Institute, University of California, Santa
Barbara, CA 93106, USA
J. Patrick, Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
G. Pepeu, Department of Preclinical and Clinical Pharmacology, University of Florence, Vide Morgagni 65, 50134
Florence, Itdy
A.G. Petrenko, Department of Molecular Genetics and Howard Hughes Medical Institute, University of Texas
Southwestern Medical Center, Dallas, TX 75235. USA
M.A.M. Prado, Department of Pharmacology and Therapeutics, McGill University, Canada and Departamento de
Bioquimica-lmunologia,U FMG, Belo Horizonte, Brazil
D.L. Price, Departments of Pathology and Neurology, and Neuroscience and Neuropathology Laboratory, The
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J. Quattrochi. Laboratory of Neurophysiology, Department of Psychiatry, Harvard Medical School, 74 Fenwood
Road, Boston, MA 021 15, USA
R. Quirion, Douglas Hospital Research Centre and Department of Psychiatry, and Departments of Pharmacology
and Therapeutics and Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal,
Quebec. Canada H4H 1R3
C. Raby. Department of Pharmacology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor,
MI 48105, USA
D.D. Rasmusson, Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada B3H 4H7
P. Reece, Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann
Arbor, MI 48105, USA
J.D. Roback, Departments of Pathology and Pharmacological and Physiological Sciences, The University of
Chicago, Chicago, IL 60637, USA
J. Robbins, Department of Pharmacology, University College London, Gower Street, London WClE 6BT, UK
G. Rodriguez de Lores Arnaiz, lnstituto de Biologia Celular, Facultad de Medicina, Universidad de Buenos Aires,
Paraguay 2155, 1121 Buenos Aires, Argentina
G.A. Rogers, Department of Chemistry and the Neuroscience Research Institute, University of California. Santa
Barbara, CA 93106, USA
G. Russi, Laboratory of Cholinergic Neuropharmacology. lstituto di Ricerche Farmacologiche "Mario Negri".
Milan, Italy
R.J. Rylett, Department of Physiology, University of Western Ontario and The Robart's Research Institute,
London, Ontario, Canada
R. Salin-Pascud. Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0603 and San
Diego Veterans Affairs Medical Center, San Diego, CA, USA
P.M. Salvaterra, Division of Neurosciences, Beckman Research Institute of the City of Hope, 1450 E. Duarte
Road, Duarte, CA 91010, USA
B.M. Schmidt, Department of Physiology, The University of Western Ontario, London, Ontario, Canada
R. Schwarz. Department of Pharmacology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann
Arbor, MI 48105, USA
O.U. Scremin. West Los Angeles VA Medical Center and Department of Physiology, UCLA School of Medicine,
Los Angeles, CA 90024, USA
P. SCquCla, Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
P. Shiromani, Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0603 and San
Diego Veterans Affairs Medical Center, Sm Diego, CA, USA
A.M. Sillito, Department of Visual Science, Institute of Ophthalmology, Bath Street, London EClV 9EL. UK
I. Silman, Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
H. Soreq, Department of Biological Chemistry, The Life Sciences Institute, The Hebrew University of Jerusalem,
Jerusalem, 91904, Israel
T.L. Steininger, Departments of Pathology and Pharmacological and Physiological Sciences, The University of
Chicago, Chicago, IL 60637. USA
M. Steriade, Laboratoire de Neurophysiologie. Facult6 de MCdecine, UniversitC Laval, Quebec, Canada, G1 K 7P4
M. Stemfeld, Department of Biological Chemistry, The Life Sciences Institute, The Hebrew University of
Jerusalem, Jerusalem. 91904, Israel
ix
T.C. Siidhof, Department of Molecular Genetics and Howard Hughes Medical Institute, University of Texas
Southwestern Medical Center, Dallas, TX 75235, USA
K. Sugaya, Department of Neuroscience, Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194, Japan
J. Sussman, Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
A. Tandon, Department of Pharmacology and Therapeutics, McGill University, Canada
A.H. Tang, CNS Diseases Research, The Upjohn Company, Kalamazoo, MI, USA
H. Tecle, Department of Chemistry, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor, MI
48105, USA
S. Tubk, Institute of Physiology, Czech Academy of Sciences, 14220 Prague, Czech Republic
J. Velaquez-Moctezuma, Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0603
and San Diego Veterans Affairs Medical Center, San Diego, CA, USA
S. Vernino, Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
M.T. Vilar6, Centro Investigacidn y Desmollo, Consejo Superior de lnvestigaciones Cientfficas, Jordi Girona,
18-26,08034 Barcelona, Spain
B.H. Wainer, Departments of Pathology and Pharmacological and Physiological Sciences. The University of
Chicago, Chicago, IL 60637, USA
V.P. Whittaker, Arbeitsgruppe Neurochemie des Anatomischen Instituts der Johannes Gutenberg-Universitat
Mainz. Postfach 3980, DW-6500 Mainz, Germany
L.R. Williams, CNS Diseases Research, The Upjohn Company, Kalamazoo, MI, USA
C.D. Woody, Mental Retardation Research Center, Departments of Anatomy and Psychiatry, UCLA Center for
Health Sciences, Los Angeles, CA 90024, USA
N.J. Woolf, Laboratory of Chemical Neuroanatomy, Department of Psychology, University of California, Los
Angeles, CA 90024-1563, USA
L. Zaborszky, Department of Neurology, University of Virginia, Charlottesville. VA, USA
M. Zambelli, Laboratory of Cholinergic Neuropharmacology, Istituto di Ricerche Farmacologiche "Mario Negri",
Milan, Italy
R. Zoltoski, Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0603 and San
Diego Veterans Affairs Medical Center, San Diego, CA, USA
xi
Preface
This book represents a rather comprehensive update of central cholinergic mechanisms from their
basic molecular aspects to possible clinical applications modifying cholinergic neurotransmission. The
reviews featured in this volume were part of formal presentations, overviews and discussions enter-
tained at the 8th International Cholinergic Symposium held in July 1992 in Ste. Adele, Quebec,
Canada. The meeting attracted a considerable number of high-calibre scientists from several conti-
nents.
The reunions are part of a series of international conferences on cholinergic transmission held
regularly every three years since the first gathering took place in 1970 in Skokloster, Sweden, organ-
ized by Professor Edith Heilbronn of Stockholm University. The “Cholinergic Club” has since then
gathered at Boldern (1974), La Jolla (1 977), Florence (1 980), Oglebay (1 983) and Buxton (1986). The
meeting preceding the Canadian conference took place in Stockholm in 1989, and was organized by
Professor Sten-Magnus Aquilonius as part of the Nobel Symposia series. Professor Konrad Lijffelholz
will organize the next symposium to be held in 1995 in Mainz, Germany.
Each one of the gatherings tended to emphasize a particular aspect of the wide-ranging field of
central and peripheral neurotransmission. For this meeting, we concentrated on CNS cholinergic
function and dysfunction, and the themes dealt with are faithfully reflected in the book’s chapters. Our
discussions covered the following subjects: organization of central cholinergic systems, CNS distribu-
tion of receptors, molecular aspects of receptors, molecular biology of cholinesterases, synthesis and
storage of ACh, ACh turnover and release, molecular aspects of ACh release, trophic interactions,
electrophysiological aspects of cholinergic mechanisms, second messengers, modulation of informa-
tion, behavioural aspects of cholinergic transmission, cholinergic involvement in sleep and arousal,
and clinical aspects of cholinergic pharmacology with special emphasis on Alzheimer’s disease.
Most of us felt that this gathering was a positive scientific experience, and as convener of the
meeting I have the pleasant duty of thanking and acknowledging all those who made it such a success.
I should start by thanking the Local Organizing Committee composed of Drs. Paul Clarke, Brian
Collier, Robert Dykes, Serge Gauthier, Kresimir Krnjevit and Remi Quirion, all of whom undertook
innumerable consultations with colleagues and the International Advisory Board to compose a most
imaginative and well-represented scientific programme. I am personally, and on behalf of the
“Cholinergic Club”, particularly grateful to Brian Collier, Remi Quirion and Paul Clarke for their
overwhelming ability to cope with organizational and fund-raising challenges.
The Secretariat of the McGill University Department of Pharmacology and the financial admini-
stration at the Douglas Hospital also had an important impact on the meeting’s effective outcome. In
addition, the symposium benefitted from the dedication, enthusiasm and charm of Ms. Anne Barry and
Ms. Marsha Warmuth. Their most efficient support was appreciated by all.
The symposium’s success was also ensured by the fine coordination of a “task force” led by Drs.
Paul Clarke, Dusica Maysinger, Maryka Quik and Sharon Welner, who were assisted by some excel-
lent graduate students from the McGill Departments of Pharmacology and Therapeutics, Neurology
and Neurosurgery and Physiology and the Douglas Hospital Research Centre.
We have been praised for the programme assembled. In turn, I would like to commend not only the
Organizing Committee, but also the supportive International Advisory Board composed of the follow-
ing members: Drs. S.-M. Aquilonius, D. Biesold, Sir Arnold Burgen, L.L. Butcher, J.-P. Changeux, E.
Costa, S. Dunnett, H.C. Fibiger, A. Fine, E. Giacobini, I. Hanin, E. Heilbronn, L.L. Iversen, S.D,
Iversen, D.J. Jenden, A.G. Karczmar, H. Ladinsky, D.A. McCormick, T. Nabeshima, J.M. Palacios,
Sir William D.M. Paton, G.P epeu, G. Rodriguez de Lores Amaiz, R.J. Rylett, H. Soreq, M. Steriade,
xii
S. TuEek and V.P. Whittaker. In particular, I would like to extend special thanks to three veterans of
the “Cholinergic Club”, Drs. Alexander Karczmar, Giancarlo Pepeu and Victor Whittaker, whose
interest, enthusiasm and insight added a valuable dimension to our discussions.
The meeting could not have been a success were it not for the support of a large list of sponsors
such as the following. Major sponsors: Astra Arcus AB (Sweden), Bayer AG (Germany), Bristol-
Myers Squibb (USA), Daiichi Pharmaceutical Co. (Japan), DuPont Pharma (USA), Fonds de la
Recherche en SantC du QuCbec, Institut de Recherche Jouveinal (France), International Society for
Neurochemistry, Kabi Pharmacia (Sweden), McGill University Faculty of Medicine and Department
of Pharmacology and Therapeutics, Medical Research Council of Canada, Merck Sharp & Dohme
Research Lab, Merck Frosst Canada Inc., MileslBayer Inc. (USA), Nordic Research (Canada), Parke
DavisWarner Lambert (USA), Sandoz Canada Inc., Savoy Foundation (Canada), Tsukuba Research
Laboratories (Japan), UNESCO/IBRO, Upjohn Canada, and US Army Medical Research Acquisition.
Sponsors: Alzheimer’s Disease Association (USA), Banyu Pharmaceutical Co. (Japan), Bio-MBga
IdBoehringer Ingelheim (Canada), Chugai Pharmac USA Inc., Ciba-Geigy Canada Ltd., Ciba-Geigy
Corp. (USA), Dainippon Pharmaceutical Co. (Japan), Douglas Hospital Research Centre, DuPont
Merck Pharmaceutical Co. (USA), Eisai Co. Ltd. (Japan), Fujisawa Pharmaceutical Co. (Japan), Glaxo
Canada Inc., Hoechst (Japan), Hoechst Celanese Corp. (USA), HoechstlRoussel Pharma (USA),
Hoffmann-LaRoche (Canada), ICI-Pharma Ltd. (Japan), ICI Pharmaceuticals Group (USA), Janssen-
Kyowa Co. (Japan), Kanebo Pharmaceuticals Ltd. (Japan), Karl Thomae GmbH (Germany), Kirin
Brewery Company Ltd. (Japan), Kowa Company (Japan), Kyowa Hakko Kogyo (Japan), Nippon
Shinyaku Co. Ltd. (Japan), Otsuka Pharmaceutical Co. (Japan), Sankyo Co. Ltd. (Japan), Santen
Pharmaceutical Co. (Japan), Sapporo Breweries Ltd. (Japan), Schering-Plough Research (USA),
Servier Canada Inc., Shionogi & Co. Ltd. (Japan), Taisho Pharmaceuticals Co. (Japan), Takeda
Chemical Industries (Japan), The Upjohn Company (USA), Tokyo Tanabe Co. Ltd. (Japan), Toyo
Jyozo Co. (Japan), Wyeth-Ayerst (USA), Yamanouchi Pharmaceutical Co. Ltd. (Japan). Donations
were also received from: Abbott Laboratories (USA), American Cyanamid Company (USA), DuPont
Canada Inc., MariodMerrell Dow Pharmaceutical Inc., Pfizer Central Research (USA) and Syntex
Research (USA).
I was most impressed by the high level of interest and cooperation obtained equally from young
scientists, students and well-established towering figures in the cholinergic area. Indeed, the meeting
was held under the honorary presidencies of Drs. W.S. Feldberg and F.C. MacIntosh, whose
pioneering contributions and exemplary lives enriched the field’s development enormously.
Since the meeting’s close in July, we sadly lost “Hank” MacIntosh, a close friend and colleague to
many of us. In this book, Brian Collier has written a fitting eulogy in remembrance of a man we val-
ued so highly.
The profiles of Drs. Numa and De Robertis were also remembered by “Cholinergic” colleagues
during the meeting, and in this volume we have included a few words about Shosaku Numa written by
Dr. Herbert Ladinsky.
The assembly of this book was aided not only by the enthusiastic response of contributors, but also
by the tenacious and highly professional participation of Marsha Warmth. Finally, I would like to
thank Elsevier and in particular, Dr. Nello Spiteri, Carien van Hooff and Tine Peereboom for their in-
terest in the subject and support of this enterprise.
A. Claudio Cuello
xiii
In memoriam
Shosaku Numa
1929-1 992
Photograph courtesy of Dr. Shigeuda Nakanishi, Kyoto, Japan.
Shosaku Numa, one of the foremost molecular biologists of his era, died from cancer on February 15,
1992 shortly after his sixty-third birthday still at the height of his scientific creativity. Numa pioneered
the use of recombinant DNA technology to reveal the molecular structure of receptors and ion
channels in excitable membranes, and has become a legend in his time. A tribute to him is particularly
appropriate in this volume on cholinergic mechanisms for he was the most prominent figure in the
study of the molecular basis of the functional diversity of acetylcholine receptors. Numa with his
