Muscarinic Receptor Subtypes in the G I Tract
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2 Muscarinic Receptor Subtypes in the G I Tract Edited by G. Lux and E. E. Daniel With 46 Figures and 13 Tables Springer-Verlag Berlin Heidelberg New York Tokyo
3 Prof. Dr. med. Gerd Lux Medizinische Klinik mit Poliklinik der UniversiUit Erlangen-Niirnberg KrankenhausstraBe 12, Erlangen, FRG Dr. E. E. Daniel Department of Neurosciences McMaster University Medical Centre 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada ISBN-I3: e-isbn-13: DOl: / Library of Congress Cataloging-in-Publication Data. Main entry under title: Muscarinic receptor SUbtypes in the GI tract. Includes index. 1. Muscarinic receptors. 2. Gastrointestinal system - Innervation. I. Lux, G. II. Daniel, E. E. [DNLM: 1. Gastrointestinal System. 2. Receptors, Muscarinic. WL M985] QP364.7.M ' This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under 54 of the German Copyright Law where copies are made for other than private use a fee is payable to,verwertungsgesellschaft Wort', Munich. Springer-Verlag Berlin Heidelberg 1985 Softcover reprint of the hardcover I st edition 1985 The use of registered names, trademarks, etc. in the publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application there of contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typesetting, printing and bookbinding: Appl, Wemding
4 Preface The differentiation between the muscarinic and the nicotinic effects of acetylcholine led to the subdivision of the cholinergic nervous system into two categories. Further studies showed that stimulating and inhibiting muscarinic effects could be demonstrated in different organs. For instance, gastric secretion and gastrointestinal motility are stimulated, while heart rate and the vascular musculature are inhibited. For decades, it could not be determined whether the various effects were mediated by different subgroups of muscarinic receptors, but eventually, with the availability of agonists and antagonists to muscarinic receptors, and using various techniques, the existence of at least two such subgroups could be ascertained.. Mt receptors are defined by their high affinity for the antagonist pirenzipine in comparison to M2 receptors. This subdivision of muscarinic receptors has since been proved beyond doubt by experiments in vivo and in vitro, by receptor binding studies, by histoautoradiography, and by electrophysiological studies. However, these different classes of muscarinic receptors have not been found to relate to different types of effects; instead both excitatory and inhibitory effects appear to be linked to each class. For example, excitation of gut motility and inhibition of cardiac contractile activities both appear to be mediated by M2 receptors, while excitation of some nerves in sympathetic ganglia and inhibition of some myenteric nerves may be mediated by Mt receptors. This volume contains the papers presented at a symposium in Berlin in March Scientists from Canada, the USA, Italy, Scandinavia, and the Federal Republic of Germany were present and contributed, and the combination of basic research in physiology and clinical applications proved to be particularly stimulating. We are grateful to Boehringer Ingelheim and Dr. Karl Thomae GmbH Biberach an der Riss for enabling the symposium to take place and to Springer-Verlag for publishing the results so swiftly. Hamilton, Ontario and Erlangen, FRG, June 1985 G. Lux and E. Daniel
5 Contents N.J. BUCKLEY Autoradiographic Localization of Muscarinic Receptors in the Gut A GIACHETTI, E. MONFERINI, A SCHIAVONE, R MICHELETTI, R HAMMER, and H. LADINSKY Functional and Biochemical Evidence for Muscarinic Receptor Subtypes in the Gastrointestinal Tract G. LAMBRECHT and E. MUTSCHLER Selective Inhibition of Muscarinic Receptors in Intestinal Smooth Muscle RANORTH and A SURPRENANT Muscarinic Receptors on Neurones of the Submucous Plexus.. 28 S. M. COLLINS The Muscarinic Receptor Subtype on Gastric Isolated Smooth Muscle Cells H. KILBINGER Subtypes of Muscarinic Receptors Modulating Acetylcholine Release from Myenteric Nerves S.RATTAN Ml and M2 Muscarinic Receptor Subtypes in the Lower Esophageal Sphincter D.von KLEIST, W.ROSSLER, H.-D. JANISCH, and K. E. HAMPEL Muscarinic Receptors and Exocrine Pancreatic Secretion. 52 P. C. LEDERER, R THIEMANN, A ELLERMANN, 1. RADECK, andg.lux Muscarinic M1-Receptor-Antagonists in Health and Disease
6 VIII Contents J. E.T. Fox, E.E.DANIEL, and T.J.McDoNALD Peptidergic Activation of Muscarinic Ml Inhibition in the Canine Small Intestine in Vivo R. W. STOCKBROGGER, B. H.JAUP, H.ABRAHAMSSON, and G. DOTEVALL Pirenzepine and Gastrointestinal Motility: Differential Effect of Pirenzepine in the Gut Subject Index
7 List of Contributors Abrahamsson, H., Division of Gastroenterology, Medical Department II, Sahlgrenska Hospital, University of G6teborg, S G6teborg, Sweden Buckley, N.J., Department of Anatomy and Embryology, University College London, Gower Street, London WC1E 6BT, UK Collins, S. M., Intestinal Diseases Research Unit and Program for the Study of Smooth Muscle, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada Dotevall, G., Division of Gastroenterology, Medical Department II, Sahlgrenska Hospital, University of G6teborg, S G6teborg, Sweden Ellermann, A, Medizinische K1inik mit Poliklinik der Universitat Erlangen - Ntimberg, Krankenhausstral3e 12, D-8520 Erlangen, FRG Fox, J. E. T., School of Nursing and Department of Neuroscience, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada Giachetti, A, Departments of Pharmacology and Biochemistry, Istituto De Angeli S.p.A, Via Serio, 15, Milan, Italy Hammer, R., Departments of Pharmacology and Biochemistry, Istituto De Angeli S.p.A, Via Serio, 15, Milan, Italy Hampel, K. E., Abteilung fur Innere Medizin mit Schwerpunkt Gastroenterologie, Universitats-K1inikum Charlottenburg, Spandauer Damm 130, D-1000 Berlin 19, FRG Jaup, B. H., Division of Gastroenterology, Medical Department II, Sahlgrenska Hospital, University of G6teborg, S G6teborg, Sweden Janisch, H.-D., Abteilung fur Innere Medizin mit Schwerpunkt Gastroenterologie, Universitats-K1inikum Charlottenburg, Spandauer Damm 130, D-1000 Berlin 19, FRG Kilbinger, H., Pharmakologisches Institut der Universitat Mainz, Obere Zahlbacher Stral3e 67, D-6500 Mainz, FRG
8 X List of Contributors von Kleist, D., Abteilung for Innere Medizin mit Schwerpunkt Gastroenterologie, Universitats-Klinikum Charlottenburg, Spandauer Damm 130, D-1000 Berlin 19, FRG Ladinsky, H., Departments of Pharmacology and Biochemistry, Istituto De Angeli S.p.A., Via Serio, Milan, Italy Lambrecht, G., A Natterman & Cie. GmbH, Department of Pharmacological Research, N attermannallee 1, D-5000 Koln 30, FRG Lederer, P. c., Medizinische Klinik mit Poliklinik der Universitat Erlangen-Niirnberg, KrankenhausstraBe 12, D-8520 Erlangen, FRG McDonald, T.J., Department of Medicine, University of Western Ontario, L8N 3Z5 Ontario, Canada Micheletti, R, Departments of Pharmacology and Biochemistry, Istituto De Angeli S.p.A, Via Serio, Milan, Italy Monferini, E., Departments of Pharmacology and Biochemistry, Istituto De Angeli S.p.A., Via Serio, Milan, Italy Mutschler, E., Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG North, RA, Neuropharmacology Laboratory, , Massachusetts Institute of Technology, Cambridge, MA 02139, USA Radeck, J., Medizinische Klinik mit Poliklinik der Universitat Erlangen-Niirnberg, KrankenhausstraBe 12, D-8520 Erlangen, FRG Rattan, S., Charles A Dana Research Institute and Harward Thorndike Laboratory of Beth Israel Hospital, Department of Medicine, Division of Gastroenterology, Beth Israel Hospital and Harward Medical School, 330 Brookline Avenue, Boston, MA 02215, USA Rossler, W., Abteilung for Innere Medizin mit Schwerpunkt Gastroenterologie, Universitats-Klinikum Charlottenburg, Spandauer Damm 130, D-1000 Berlin 19, FRG Schiavone, A, Departments of Pharmacology and Biochemistry, Istituto De Angeli S.p.A., Via Serio, Milan, Italy Stockbriigger, R w., Division of Gastroenterology, Medical Department II, Sahlgrenska Hospital, University of Goteborg, S Goteborg, Sweden Surprenant, A, Neuropharmacology Laboratory, , Massachusetts Institute of Technology, Cambridge, MA 02139, USA Thiemann, R, Medizinische Klinik mit Poliklinik der Universitat Erlangen-Niirnberg, KrankenhausstraBe 12, D-8520 Erlangen, FRG
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