NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NA TO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The Series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics London and New York C Mathematical and Kluwer Academic Publishers Physical Sciences Dordrecht, Boston and London D Behavioural and Social Sciences E Applied Sciences F Computer and Springer-Verlag Systems Sciences Berlin Heidelberg New York G Ecological Sciences London Paris Tokyo H Cell Biology Series H: Cell Biology Vol. 25 The ASI Series Books Published as a Result of Activities of the Special Programme on CELL TO CELL SIGNALS IN PLANTS AND ANIMALS This book contains the proceedings of a NATO Advanced Research Workshop held within the activities of the NATO Special Programme on Cell to Cell Signals in Plants and Animals, running from 1984 to 1989 under the auspices of the NATO Science Committee. The books published as a result of the activities of the Special Programme are: Vol. 1 : Biology and Molecular Biology of Plant-Pathogen Interactions. Edited by J.A. Bailey. 1986. Vol. 2: Glial-Neuronal Communication in Development and Regeneration. Edited by H.H. Althaus and W. Seifert. 1987. Vol. 3: Nicotinic Acetylcholine Receptor: Structure and Function. Edited by A. Maelicke. 1986. Vol. 4: Recognition in Microbe-Plant Symbiotic and Pathogenic Interactions. Edited by B. Lugtenberg. 1986. Vol. 5: Mesenchymal-Epithelial Interactions in Neural Development. Edited by J. R. Wolff, J. Sievers, and M. Berry. 1987. Vol. 6: Molecular Mechanisms of Desensitization to Signal Molecules. Edited by T. M. Konijn, P.J. M. Van Haastert, H. Van der Starre, H. Van der Wei, and M.D. Houslay. 1987. Vol. 7: Gangliosides and Modulation of Neuronal Functions. Edited by H. Rahmann. 1987. Vol. 9: Modification of Cell to Cell Signals During Normal and Pathological Aging. Edited by S. Govoni and F. Battaini. 1987. Vol. 10: Plant Hormone Receptors. Edited by D. Klambt. 1987. Vol. 11: Host-Parasite Cellular and Molecular Interactions in Protozoal Infections. Edited by K.-P' Chang and D. Snary. 1987. Vol. 12: The Cell Surface in Signal Transduction. Edited by E. Wagner, H. Greppin, and B. Millet. 1987. Vol. 19: Modulation of Synaptic Transmission and Plasticity in Nervous Systems. Edited by G. Hertting and H.-C. Spatz. 1988. Vol. 20: Amino Acid Availability and Brain Function in Health and Disease. Edited by G. Huether. 1988. Vol. 21: Cellular and Molecular Basis of Synaptic Transmission. Edited by H. Zimmermann. 1988. Vol. 23: The Semiotics of Cellular Communication in the Immune System. Edited by E. E. Sercarz, F. Celada, N. A. Mitchison, and~. Tada. 1988. Vol. 24: Bacteria, Complement and the Phagocytic Cell. Edited by F.C. Cabello and C. Pruzzo. 1988. Vol. 25: Nicotinic Acetylcholine Receptors in the Nervous System. Edited by F. Clementi, C. Gotti, and E. Sher. 1988. Nicotinic Acetylcholine Receptors in the Nervous System Edited by Francesco Clementi Cecilia Gotti Emanuele Sher CNR Center of Cytopharmacology Department of Medical Pharmacology University of Milano Via Vanvitelli 32 1-20129 Milano, Italy Springer -Verlag Berlin Heidelberg New York London Paris Tokyo Published in cooperation with NATO Scientific Affairs Division Proceedings of the NATO Advanced Research Workshop on Nicotinic Acetylcho line Receptors in the Nervous System held in Venice, Italy, April 18-21 ,1988 Library of Congress Cataloging-in-Publication Data. NATO Advanced Research Workshop on Nicotinic Acetylcholine Receptors in the Nervous System (1988: Venice, Italy) Nicotinic acetylcholine receptors in the nervous system 1e dited by Francesco Clementi, Cecilia Gotti, Emanuele Sher. p. cm.-(NATO ASI series. Series H, Cell biology; vol. 25) Proceedings of the NATO Advanced Research Workshop on Nicotinic Acetylcholine Receptors in the Nervous System held in Venice, Italy, April 18-21 , 1988"-T.p. verso. "Published in cooperation with NATO Scientific Affairs Division." Includes bibliographies and indexes. ISBN-13: 978-3-642-74169-2 e-ISBN-13: 978-3-642-74167-8 001: 10.1007/978-3-642-74167-8 1. Nicotinic receptors-Congresses. 2. Acetylcholine-Receptors-Congresses. I. Clementi, Francesco. II. Gotti, Cecilia. III. Sher, Emanuele. IV. North Atlantic Treaty Organization. Scientific Affairs Division. V. Title. VI. Series. [DNLM: 1. Receptors, Cholinergic-congresses. 2. Receptors, Nicotinic-congresses. WL 102.8 N2795n 1988] QP364.7.N3641988 615'.785-dc 19 DNLM/DLC for Library of Congress 88-38978 This work is subject to copyright. A!I rights are reserved, whether the whole or part of the material is concerned, specifically the rights oftranslation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication ofthis publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1988 50ftcover reprint of the hardcover 15t edition 1988 2131/3140-543210-Printed on acid-free paper - CONTENTS - PREFACE SCIENTIFIC COMMlTfEE WORKSHOP PARTICIPANTS CONFERENCE PHOTOORAPH BIOCHEMICAL AND PHARMACOLOGICAL CHARACTERIZATION OF NEURONAL NICOTINIC RECEPTORS AUTORADIOGRAPHIC MAPPING OF PUTATIVE NICOTINIC CHOLINOCEPfOR IN MAMMALIAN BRAIN P.B.S. Clarke 1 FUNCTIONAL STUDIES OF NEURONAL NICOTINIC RECEPfORS UTILIZING KAPPA-NEUROTOXINS V.A. Chiappinelli, S.E. Dryer, E.M. Sorenson, K.M. Wolf, G.A. Grant, S.-J. Chen, J.M. Nooney, J.J. Lambert and R.C. Hider 15 CHARACTERIZATION AND LOCALIZATION OF GANGLIONIC NICOTINIC RECEPfORS USING NEURONAL BUNGAROTOXIN R.E. Zigmond and R.H. Loring 31 ALPHA-BUNGAROTOXIN AND PRESYNAPTIC NICOTINIC RECEPTORS: FUNCTIONAL STUDIES S. Wonnacott, J. Irons, G.G. Lunt, C.M. Rapier and E.X. Albuquerque 41 EVIDENCE FOR FUNCTIONAL AND STRUCTURAL DIVERSITY OF NICOTINIC ACETYLCHOLINE RECEPTORS Lukas R.J. 61 BIOCHEMICAL AND MOLECULAR BIOLOGY APPROACHES TO CENTRAL NICOTINIC ACETYLCHOLINE RECEPfORS I. Hermans-Borgmeyer, E. Sawruk, P. Schloss, E.D. Gundelfinger and H. Ben 77 ALPHA-BUNGAROTOXIN RECEPfOR IN A HUMAN NEUROBLASTOMA CELL LINE C. Gotti, E. Sher, D. Fornasari, B. Chini, A. Esparis Ogando, F. Clementi 89 CHARACTERIZATION OF THE ALPHA-BUNGAROTOXIN BINDING PROTEIN FROM PC12 CELLS G. Kemp 105 IDENTIFICATION OF SURFACE DOMAINS OF THE NICOTINIC ACETYLCHOLINE RECEPfOR MOLECULE BY THE USE OF ANTIBODIES AND TOXINS. B.M. Conti-Tronconi, A. Kokla, A. Maelicke, R. Milius, M.A. Raftery, S.R. Spencer, F. Tang and S. Tzartos 119 HETEROGENEITY OF NICOTINE ACTIONS IN THE RAT CEREBELLUM R. de La Garza, B.J. Hoffer, and R. Freedman 137 VI DISTRIBUTION OF NICOTINIC RECEPTORS IN THE HUMAN BRAIN: QUANTITATIVE AUTORADIOGRAPHY USING 3H-NICOTINE A. Adem, P.-G. Gillberg, S.S. Jossan, V. Sara and A. Nordberg 143 DISTRIBUTION OF 3H-N-METHYLCARBAMYLCHOLINE BINDING SITES IN RAT BRAIN: CORRELATION WITH NICOTINIC AUTORECEPTORS. P.A. Lapchak, D.M. Araujo, R. Quirion, B. Collier 149 MOLECULAR BIOLOGY OF AChR STRUCfURE OF NEURONAL NICOTINIC RECEPTORS J. Lindstrom, P. Whiting, R. Schoepfer, M. Luther and B. Casey 159 THE NICOTINIC ACETYLCHOLINE RECEPTOR GENE FAMILY S. Heinemann, J. Boulter, E. Deneris, J. Connolly, P. Gardner, E. ".' Wada, K. Wada, M. Ballivet, L. Swanson and J. Patrick 173 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR GENES IN THE AVIAN GENOME P. Nef, C. Oneyser, C. Alliod, S. Couturier and M. Ballivet 193 INVERTEBRATE AChR NICOTINIC ACETYLCHOLINE RECEPTORS IN INSECT GANGLIA AND MAM MALIAN BRAIN: SOME COMPARISON D.R.E. Macallan, S. Wonnacott and G.G. Lunt 199 IDENTIFICATION OF NICOTINIC ACETYLCHOLINE RECEPTORS FROM THE NERVOUS SYSTEM OF INSECTS H. Breer and W. Hanke 213 PHARMACOLOGY OF A LOCUST THORACIC GANGLION SOMAL NICOTINIC ACETYLCHOLINE RECEPfOR J.A. Benson 227 SYNAPTIC AND EXTRASYNAPTIC NEURONAL NICOTINIC RECEPTORS OF INSECTS D. B. Sattelle 241 PHARMACOLOGY, CLONING AND EXPRESSION OF INSECT NICOTINIC ACEfYLCHOLlNE RECEPTORS J. Marshall, J.A. David, M.G. Darlison, E.A. Barnard and D.B. Sattelle 257 AChR INVOLVEMENT IN PHYSIOLOGY AND PATHOLOGY REGULATION OF NEURONAL ACETYLCHOLINE RECEPTORS BY CELL-CELL INTERACTIONS D.K. Berg, R.T. Boyd, S.W. Halvorsen, L.S. Higgins, M.H. Jacob, J.F. Margiotta and A.E. McEachern 283 VII PHARMACOLOGICAL MODULATION OF BRAIN NICOTINIC BINDING SITES L.G. Costa 299 REGULATION OF BEHAVIORAL AND PHYSIOLOGICAL SENSITIVITY TO NICOTINE BY BRAIN NICOTINIC RECEPTORS A.G. Collins and M.J. Marks 317 HEfEROGENEOUS CHOLINERGIC NICOTINIC RECEPTORS IN THE CNS A. Nordberg, A. Adem, L. Nilsson, L. Romanelli and X. Zhang 331 CHOLINERGIC NEUROPATHOLOGY AND NICOTINIC RECEPTOR BINDING IN THE HUMAN BRAIN E.K. Perry, C.J. Smith, l.H.Xuereb, A.B. Keith, R.H. Perry 351 THE CHOLINERGIC RECEPTOR SYSTEM IN THE FRONTAL LOBE OF ALZHEIMER PATIENTS E. Giacobini, P. De Sarno, M. Mcllhany, B. Clark 367 DEVELOPMENTAL REGULATION AND MODULATION OF NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR CHANNELS L.K. Simmons, B.L. Moss, S.M. Schuetze and LW. Role 379 IMMUNOCYTOCHEMICAL LOCALIZATION OF NICOTINIC RECEPTORS IN THE FROG RETINA: PHYSIOLOGICAL CORRELATES N. Bonaventure, B. lardon, 1. Sahel, G. Roussel and H. Yucel 393 AUTHORS INDEX 409 SUBJEcrs INDEX 411 PREFACE The acetylcholine nicotinic receptor is an ionic channel whose aperture is directly controlled by acetylcholine. It is a key molecule in the chemical communication between nerve cells and between nerve cell and muscle. The structure and function of muscular nicotinic receptors have been unraveled in recent years and its beauty and mysteries were reviewed in the Santorini NATO ARW organized by Dr. Maelicke in 1986. The neat, linear structure of this molecule and its conservation throughout evolution, from bacteria to humans, have led to the suggestion that it has reached the optimal structure for performing its function. But when scientists began to look at the nicotinic receptor in the nervous system, they found several surprises. From the beginning, pharmacological and physiological experiments, have made it clear that the functional characteristics of neuronal nicotinic receptors are substantially different from those of muscle receptors. Furthermore, recent sophisticated techniques such as patch clamp and gene cloning have revealed that the nicotinic receptor in the nervous system is not a single molecule but (although there are some important exceptions) a large family of similar molecules, which have in common the property of binding nicotinic agonists or antagonists. Over the last few years, the physiological implications of nicotinic receptors have been reevaluated on the basis of more precise behavioural and pharmacological techniques. Moreover, the involvement of nicotinic receptors in degenerative pathologies of the eNS, such as Parkinson's and Alzheimer's disease, has also been discovered very recently. In collaboration with Drs. Eric Barnard and Hans Breer, we thought that the time had come to gather together all the scientists working on the nicotinic receptors of the nervous system (from molecular biologists to physiologists, from pharmacologists to clinicians) in order to clarify the basic characteristics of the molecule and to open up new lines of research. Our scientific knowledge would certainly be extended in a shorter time if everyone worked together. The Venice workshop held in the superb palazzo of the Fondazione Querini Stampalia and sponsored by the Fondazione Emilio Trabucchi was an ideal setting for an informal and fruitful meeting. Representatives from nearly all the laboratories working on this subject were present and the atmosphere of Venice itself helped to create the appropriate conditions for informal discussion and the establishement of friendly relations. IX The valuable contributions presented at the meeting are collected in this book. It will certainly become the basic reference work for scientists active in the field of the nicotinic receptors of the nervous system, since it contains the most up to date information about the different scientific aspects of this fascinating new area, written by the most experienced researchers in the field. The meeting was made possible by a substantial grant from the NATO Special Program on Cell-to-Cell Signals, and by the generous support of Fidia Research Laboratories. Our stay in Venice was organized by the expert of Venetian life, Dr. Giorgio Busetto, Director of the Fondazione Querini Stampalia, and his staff who opened palazzo Querini to "nicotinic" scientists, suggested the social program .and contacted local organizations. Mrs. Ida Ruffoni in particular, but also all the other colleagues from our laboratory, contributed with their enthusiasm and dedication, to creating the atmosphere and the success of the meeting. We are also indebted to the CNR (the Italian National Research Council), the Regional authorities of Veneto and the local authorities of Venice, Crinos SpA, ISF SpA, Italfarmaco, Sigma Tau and Zambon SpA, which made our life as organizers easier and the stay of the scientists attending the meeting more pleasant. We hope that this meeting has opened the way for a long and exciting series of future adventures in the discovery of the still mysterious facets of these molecules. Francesco Clementi Cecilia Gotti August 1, 1988. Emanuele Sher Scientific committee Eric A. Barnard MRC Mol. Neurobiology Unit University of Cambridge Medical School Cambridge, England Hans Breer Dept. of Physiology University of Osnabruck Osnabruck, FRG Francesco Clementi Dept. of Pharmacology University of Milan Milan, Italy Cecilia Gotti CNR Center of Cytopharmacology University of Milan Milan, Italy Emanuele Sher CNR Center of Cytopharmacology University of Milan Milan, Italy