Primer on the Autonomic Nervous System This. Page Intentionally Left Blank Primer on the Autonomic Nervous System Editor in Chief David Robertson Vanderbilt University Editors Italo Biaggioni Vanderbilt University Geoffrey Burnstock Royal Free & University College London Phillip A. Low The Mayo Clinic AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Elsevier Academic Press 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald’s Road, London WC1X 8RR, UK This book is printed on acid-free paper. ᭺• Copyright © 2004, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://elsevier.com), by selecting “Customer Support” and then “Obtaining Permissions.” Library of Congress Cataloging-in-Publication Data Primer on the autonomic nervous system / editor in chief, David Robertson; editors, Italo Biaggioni, Geoffrey Burnstock, Phillip A. Low.—2nd ed. p. ; cm. Includes bibliographical references and index. ISBN 0-12-589762-6 1. Autonomic nervous system—Diseases. 2. Autonomic nervous system—Physiology. I. Robertson, David, 1947– [DNLM: 1. Autonomic Nervous System Diseases—physiopathology. 2. Autonomic Nervous System—physiology. WL 600 P953 2004] RC407.P75 2004 616.8¢56—dc22 2003070923 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN: 0-12-589762-6 For all information on all Academic Press publications visit our Web site at www.academicpress.com Printed in the United States of America 040506070809 987654321 Contents List of Contributors xix Noradrenaline Phenotype 9 Preface xxvii Control Mechanism of DBH Gene Expression Is Closely Related to Autonomic Nervous System Development 9 PART Cholinergic Phenotype and the Switch of Neurotransmitter I Phenotypes by the Target Cell Interactions 9 3. Milestones in Autonomic Research ANATOMY MAX R. BENNETT 1. Development of the Autonomic Receptors 12 Nervous System Classical Transmitters: The Discovery of Noradrenaline, Acetylcholine, and Their Receptors 12 CARYL E. HILL The Discovery of New Transmitters, Including Nucleotides, Peptides, and Nitric Oxide 12 Pathways and Fate of Neural Crest Cells 3 Varicosities 12 Factors Operating during Neural Crest Migration 3 Varicosities Shown to be the Source of Transmitters 12 Neurite Outgrowth and Target Contact 4 Varicosities Have the Capacity to Take Up Transmitters Factors Involved in Neurite Outgrowth and Neuronal After Their Release 12 Survival 5 Varicosities Possess Receptors That on Activation Modulate Synapse Formation and Neuronal Differentiation 5 Further Transmitter Release 13 Conclusions 5 Generation of Currents and Second Messengers on Receptor Activation After Transmitter Release from Varicosities 13 2. Mechanisms of Differentiation of Action Potentials, Initiated by the Generation of Junction Autonomic Neurons Potentials, Are Caused by the Influx of Calcium Ions 13 KWANG-SOO KIM Control of the Influx of Calcium Ions Is a Principal Means of Decreasing Blood Pressure 13 The Autonomic Nervous System Is Derived from Neural Crest Cells 6 PART Signaling Molecules Regulate the Developmental Processes of the Autonomic Nervous System 6 II Transcriptional Code Underlying the Development and Phenotypic Specification of the Autonomic PHARMACOLOGY Nervous System 7 Mash1 7 Phox2 Genes 7 4. Central Autonomic Control Gata3 8 EDUARDO E. BENARROCH Activator Protein 2 8 Other Transcriptional Factors 8 Anatomy of Central Autonomic Areas 17 Neurotransmitter Phenotypes of the Autonomic Forebrain 17 Nervous System 9 Levels of Integration of Central Autonomic Control 18 v vi Contents Bulbospinal Level 18 9. Dopamine Receptors Pontomesencephalic Level 18 AKI LAAKSO AND MARC G. CARON Forebrain Level 18 Structural and Functional Characteristics of 5. Peripheral Autonomic Nervous System Dopamine Receptors 39 Gene Structure 39 ROBERT W. HAMILL AND ROBERT E. SHAPIRO Receptor Structure 39 Signal Transduction 40 Sympathetic Nervous System 20 D1-like Receptors 40 Sympathoadrenal Axis and the Adrenal Gland 23 D2-like Receptors 41 Parasympathetic Nervous System 24 Oligomerization 41 The Concept of Plurichemical Transmission and Pharmacology 42 Chemical Coding 25 Distribution 42 Functional Neuroanatomy and Biochemical Distribution in the Brain 42 Pharmacology 27 D1 Receptors 42 D2 Receptors 42 D3 Receptors 42 6. The Autonomic Neuroeffector Junction D4 Receptors 43 GEOFFREY BURNSTOCK D5 Receptors 43 Dopamine Receptors in the Periphery 43 Structure of the Autonomic Neuromuscular Junction 29 Regulation 43 Varicose Terminal Axons 29 Junctional Cleft 29 Prejunctional and Postjunctional Specialization 30 10. Noradrenergic Neurotransmission Muscle Effector Bundles and Gap Junctions 30 DAVID S. GOLDSTEIN Autonomic Neurotransmission 30 Electrophysiology 30 Noradrenergic Innervation of the Cardiovascular Receptor Localization on Smooth Muscle Cells 31 System 44 Model of Autonomic Neuroeffector Junction 32 Norepinephrine: The Sympathetic Neurotransmitter 45 Norepinephrine Synthesis 45 7. Autonomic Neuromuscular Transmission Storage 46 Release 46 MAX R. BENNETT Disposition 47 New Transmitters and the Concept of Cotransmitters 34 Varicosities, Vesicle-Associated Proteins, and 11. a -Adrenergic Receptors Calcium Fluxes 34 1 Ionotropic Receptors Are Localized to the Muscle ROBERT M. GRAHAM Membrane at Varicosities 34 Subtypes 50 Metabotropic and Ionotropic Receptors Are Structure and Signaling 50 Internalized and Recycled after Binding Ligand Binding and Activation 50 Transmitter 34 Regulation 52 Sources of Intracellular Calcium in Smooth Muscle Vascular Subtypes 52 for Initiating Contraction 35 Modulation of Calcium Influx and the Control of Hypertension 35 12. a2-Adrenergic Receptors LEE E. LIMBIRD 8. Dopaminergic Neurotransmission CHRISTOPHER BELL 13. b-Adrenergic Receptors Transmitter Neurochemistry 36 STEPHEN B. LIGGETT Transmitter Synthesis 36 Transmitter Storage and Release 36 Signaling of b-AR Subtypes 57 Transmitter Recycling 36 Regulation of b-AR Function 57 Future Questions 37 Polymorphisms of b-AR 58 Contents vii 14. Purinergic Neurotransmission 18. Acetylcholinesterase and Its Inhibitors GEOFFREY BURNSTOCK ALBERT ENZ Sympathetic Nerves 61 Mechanism of Action 77 Parasympathetic Nerves 61 Acetylcholinesterase Inhibitors 77 Sensory-Motor Nerves 62 Pharmacologic Actions of Acetylcholinesterase Intramural (Intrinsic) Nerves 63 Inhibition 77 Skeletal Neuromuscular Junctions 63 Clinical Applications of Anticholinesterases 79 Synaptic Purinergic Transmission in Ganglia and Cholinesterase Inhibitors and Alzheimer’s Disease 80 Brain 64 Glial Cells 64 Plasticity of Expression of Purinergic Cotransmitters 64 Long-Term (Trophic) Signaling 64 19. Amino Acid Neurotransmission WILLIAM TALMAN P2X3 Receptors and Nociception 64 Future Developments 64 20. Peptidergic Neurotransmission 15. Adenosine Receptors and GRAHAM J. DOCKRAY Autonomic Regulation Families of Peptide Transmitters 83 ITALO BIAGGIONI Generic Features of Peptidergic Transmission 83 Biosynthesis 83 Postsynaptic Antiadrenergic Effects of Adenosine 66 Storage and Release 83 Presynaptic Effects of Adenosine on Efferent Nerves Receptors 84 and Ganglionic Transmission 66 Degradation 84 Adenosine and Central Autonomic Regulation 66 Chemical Coding 84 Neuroexcitatory Actions of Adenosine on Afferent Overview of Peptides in the Autonomic Nervous Pathways 67 System 84 Integrated View of Adenosine and Cardiovascular Autonomic Regulation 67 21. Leptin Signaling in the Central Nervous System 16. Acetylcholine and Muscarinic Receptors KAMAL RAHMOUNI, WILLIAM G. HAYNES, AND ALLYN L. MARK B. V. RAMA SASTRY AND DAVID ROBERTSON Central Neural Action of Leptin 86 Acetylcholine Synthesis and Metabolism: Drug Leptin Receptor 86 Mechanisms 70 Intracellular Mechanisms of Leptin Signaling 86 Acetylcholine Receptors 70 Site of Leptin Action in the Brain 87 Muscarinic Agonists 71 Interaction of Leptin and Neuropeptides in the Muscarinic Autonomic Effects of Acetylcholine 71 Hypothalamus 87 Muscarinic Antagonists 72 Neuropeptide Y 87 Melanocortin System 88 Other Mediators 88 Conclusion 89 17. Nicotinic Acetylcholine Receptors: Structure and Functional Properties PALMER TAYLOR 22. Nitrergic Neurotransmission JILL LINCOLN Structural Considerations 73 Subtype Diversity of Nicotinic Receptors 73 Synthesis of Nitric Oxide 90 Electrophysiologic Events Associated with Receptor Mechanisms of Nitrergic Neurotransmission 90 Activation 74 Nitrergic Neurotransmission in the Autonomic Nervous Distribution of Nicotinic Receptors 76 System and Pathologic Implications 91 viii Contents 23. Serotonin Receptors and 29. Gastrointestinal Function Neurotransmission MICHAEL CAMILLERI ELAINE SANDERS-BUSH AND CHARLES D. NICHOLS Salivary Secretion 118 Localization 93 Gastric Secretion 118 Synthesis and Metabolism 93 Pancreaticobiliary Secretion 118 Neurotransmission 93 Bile 118 Receptors 94 Intestinal Secretion and Absorption 119 Pharmacology and Role in Disease 94 Control of Gut Motility 119 Normal Gastrointestinal Motor Function