Motilin. Edited by. Zen Itoh. Gastrointestinal Laboratories College of Medical Technology Gunma University Maebashi, Japan

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1 Motilin Edited by Zen Itoh Gastrointestinal Laboratories College of Medical Technology Gunma University Maebashi, Japan Academic Press, Inc. Harcourt Brace Jovanovich, Publishers San Diego New York Berkeley Boston London Sydney Tokyo Toronto

2 Contributors Preface xv xi 1. Introduction Vay Liang W. Go Text 1 References 3 2. The Discovery of Motilin J. C. Brown and C. H. S. Mclntosh Text 5 References Purification and Chemical Structure of Porcine and Canine Motilins and Evidence for the Existence of Motilin in Other Species C. H. S. Mclntosh and J. C. Brown I. Isolation of Porcine Motilin 13 II. Amino Acid Composition and Sequence Analysis of Porcine Motilin 16 III. Isolation of Canine Motilin 19 IV. Amino Acid Composition and Sequence Analysis of Canine Motilin 20 V. Motilin in Other Species 22 VI. Heterogeneity of Motilin 24 VII. Structure-Activity Relationships 25 References Chemical Synthesis, Radioimmunoassay, and Distribution of Immunoreactivity of Motilin Noboru Yanaihara, Chizuko Yanaihara, Tohru Mochizuki, Kazuaki Iguchi, and Minoru Hoshino I. Introduction 31 II. Chemical Synthesis 32

3 Vi III. Radioimmunoassay 35 IV. Distribution of Immunoreactivity 41 References Prohormone of Human Motilin Yutaka Seino, Jun Takeda, and Hiroo Imura I. Heterogeneity of Human Motilin (porcine motilin) 47 II. Isolation and Characterization of a Motilin cdna Clone 48 III. Primary Structure of Human Prepromotilin 48 IV. Comparison of Motilin Sequence 50 References Morphological Identification of Motilin in the Gut Shigeru Kobayashi and Takashi Uchida I. Immunocytochemical Demonstration of Motilin-Containing Cells 53 II. Immunocytochemical Controls 56 III. Enterochromaffin Cells and Motilin 57 IV. Structure and Ultrastructure of the Mo Cells 60 V. Transportation Route of Motilin in the Lamina Propria Mucosae 63 VI. Phylogeny, Ontogeny, and Kinetics 64 VII. Mo Cells in the Segi's Cap 67 References Mechanisms of Motilin Excitation as Determined by in Situ and in Vitro Studies J. E. T. Fox I. Introduction 73 II. Sites and Mechanisms of Action 75 III. Conclusion 88 References Motilin Receptors T. L. Peeters, G. Vantrappen, and I. Depoortere I. Introduction 93 II. Search for Motilin Binding Sites 94 III. Characterization of Motilin Binding 97 IV. Localization of Motilin Receptors 101 V. Regulation and Development 103 VI. Motilin Agonists 104 VII. Conclusions 105 References 106

4 9. Biological Activity of Motilin in Gastric, Pancreatic, and Duodenal Secretion StanislawJ. Konturek, Jan W. Konturek, Piotr Thor, and Jolanta Jaworek I. Introduction 111 II. Distribution and Release of Motilin as Related to Gastrointestinal Motilin 112 III. Mechanism of Action 112 IV. Secretory Component of Migrating Motor Complex 114 V. Motilin and Gastroduodenal Secretion 114 VI. Motilin and Pancreatic and Biliary Secretion 119 VII. Summary and Conclusion 123 References Biological Activity in Gastric Emptying Takeo Yamagishi and Haile T. Debas I. Introduction 127 II. Normal Regulation of Gastric Emptying 127 III. Effect of Motilin on Gastric and Duodenal Smooth Muscle in Vitro 128 IV. Effect of Motilin on Myoelectric and Contractile Activity in Vivo 129 V. Effect of Motilin on Gastric Emptying in Animals 129 VI. Effect of Motilin on Gastric Emptying in Humans 130 References Effect of Motilin on Gastrointestinal Motor Activity in the Dog Zen Itoh I. Introduction 133 II. Materials and Methods 136 III. Results 139 IV. Discussion and Conclusion 149 References Role of Motilin in Biliary Tract Physiology Torgny Svenberg and Jugemar Nilsson I. Introduction 155 II. Physiological Background 155 III. Effects of Exogenous Motilin Infusions on the Biliary Tract in Vivo or in Vitro Experiments in Animals or Humans 157 IV. Fasting Plasma Motilin Fluctuations in Relation to Interdigestive Biliary Emptying Studies in Humans 160 vii

5 viii V. Relationship between Interdigestive Biliary Emptying Motilin Release and Fasting Gastroduodenal Motility in Humans 162 VI. General Summary 166 References Endogenous Motilin Release: Physiology and Pathophysiology Kae Yol Lee and William Y. Chey I. Introduction 169 II. Plasma Motilin Concentrations in Interdigestive States 170 III. Motilin Release after Ingestion of a Meal or Fat 176 IV. Effect of Duodenal ph Changes on Motilin Release 178 V. Effects of Hormones, Peptides, and Others on Motilin Release 179 VI. Plasma Motilin Levels in Relation to Interdigestive Pancreatic Secretion 181 VII. Motilin Release in Abnormal States 182 References Mechanism of Motilin Release by Luminal Stimuli and Vagal Nerve N. E. Diamant I. Introduction 191 II. Localization of Motilin 193 III. Neural Mechanisms for Motilin Release 194 IV. Intraluminal Nutrients 196 V. Intraluminal Acid and Alkali 200 VI. Intraluminal Biliary and Pancreatic Secretions, 201 VII. Other Factors 202 References Clinical Significance of Motilin in Diseases of the Gastrointestinal Tract G. Vantrappen, T. L. Peeters, and J. Janssens I. Normal Motilinemia 209 II. Motilinemia and Gastrointestinal Dysfunction 213 III. Therapeutic Applications 218 IV. Summary and Conclusions 218 ' References 220

6 16. Gastroduodenal Motor Dysfunction and Plasma Motilin Concentration in Patients with Duodenal Ulcers Toshikazu Sekiguchi, Motoyasu Kusano, Toshio Nishioka, and Zen Itoh I. Interdigestive, Intragastric, and Duodenal ph and Motility in Normal Subjects 226 II. IMC Appearance in 24-hr Monitoring of Intragastric and Duodenal ph and Motility of Normal Subjects 229 III. Pattern of Interdigestive Gastroduodenal Motility and ph in Duodenal Ulcer Patients 229 IV. IMC in 24-hr Monitoring of Gastroduodenal Motility and ph of Duodenal Ulcer Patients 230 V. Comparison of Gastroduodenal Motility and ph in Duodenal Ulcer Patients and Normal Subjects 231 VI. Plasma Motilin Concentrations and Interdigestive Gastroduodenal Motility in Humans 234 VII. Characteristics of Plasma Motilin Behavior and IMC Appearance in Duodenal Ulcer Patients 237 VIII. Histamine H 2 Receptor Antagonist Neutralizes Intraluminal ph of the Gastroduodenum, but GI-IMC Appears after an Increase in Plasma Motilin 239 References Motilide, Motilin-like Macrolides Satoshi Omura, Yoichi Kondo, and Zen Itoh I. Introduction 245 II. Chemical Synthesis of Erythromycin Derivatives 246 III. Biological Activity 246 IV. Receptor Binding Study 253 V. Discussion and Conclusion 255 References 255 Index 257 IX

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