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VASOPRESSIN and OXYTOCIN Molecular, Cellular, and Clinical Advances ADVANCES in EXPERIMENTAL MEDICINE and BIOLOGY

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VASOPRESSIN and OXYTOCIN Molecular, Cellular, and Clinical Advances ADVANCES in EXPERIMENTAL MEDICINE and BIOLOGY VASOPRESSIN AND OXYTOCIN Molecular, Cellular, and Clinical Advances ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institutefor Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 443 ADV ANCES IN LACTOFERRIN RESEARCH Edited by Genevieve Spik, Dominique Legrand, Joel Mazurier, Annick Pierce, and Jean-Paul Perraudin Volume 444 REPRODUCTIVE TOXICOLOGY: In Vitro Germ Cell Developmental Toxicology, from Science to Social and Industrial Demand Edited by Jesus del Mazo Volume 445 MA THEMA TICAL MODELING IN EXPERIMENTAL NUTRITION Edited by Andrew J. Clifford and Hans-Georg MUlier Volume 446 MOLECULAR AND CELLULAR MECHANISMS OF NEURONAL PLASTICITY: Basic and Clinical Implications Edited by Yigal H. Ehrlich Volume 447 LIPOXYGENASES AND THEIR METABOLITES: Biological Functions Edited by Santosh Nigam and Cecil R. Pace-Asciak Volume 448 COPPER TRANSPORT AND ITS DISORDERS: Molecular aIfd Cellular Aspects Edited by Arturo Leone and Julian F. B. Mercer Volume 449 VASOPRESSIN AND OXYTOCIN: Molecular, Cellular, and Clinical Advances Edited by Harts H.Zingg, Charles W. Bourque, and Daniel G. Bichet Volume 450 ADV ANCES IN MODELING AND CONTROL OF VENTILATION Edited by Richard L. Hughson, David A. Cunningham, and James Duffin Volume 451 GENE THERAPY OF CANCER Edited by Peter Walden, Uwe Trefzer, Wolfram Sterry, and Farzin Farzaneh Volume 452 MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII: Molecular Determinants of Microbial Immunity Edited by Sudhir Gupta, Alan Sher, and Rafi Ahmed A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. VASOPRESSIN AND OXYTOCIN Molecular, Cellular, and Clinica! Advances Edited hy Hans H. Zingg and Charles W. Bourque McGill University Montreal, Quebec, Canada and Daniel G. Bichet University of Montreal Montreal, Quebec, Canada SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging in Publication Data Vasopressin and oxytocin: molecular, cellular, and clinical advances / edited by Hans H. Zingg, Charles W. Bourque, and Daniel G. Bichet. p. cm.-(Advances in experimental medicine and biology; v. 449) "Proceedings of a World Congress on Neurohypophysial Hormones, held August 8-12, 1997, Montreal, Quebec, Canada"-T.p. verso. Includes bibliographical references and index. ISBN 978-1-4613-7210-3 ISBN 978-1-4615-4871-3 (eBook) DOI 10.1007/978-1-4615-4871-3 1. Vasopressin-Congresses. 2. Oxytocin-Congresses. 1. Zingg, Hans H. II. Bourque, Charles W. III. Bichet, Daniel G. IV. World Congress on Neurohypophysial Hormones (1997: Montreal, Que­ bec) V. Series. [DNLM: 1. Vasopressins congresses. 2. Oxytocin congresses. WK 520V33393 1998] QP572.V3V 1998 612.4'92-dc21 DNLM/DLC 98-40029 for Library of Congress CIP Proceedings of a World Congress on Neurohypophysial Hormones, held August 8 - 12, 1997, in Montreal, Quebec, Canada ISBN 978-1-4613-7210-3 © 1998 by Springer Science+Business Media New York OriginallY published by Plenum Press New York in 1998 Softcover reprint of the hardcover 1st edition 1998 http://www.plenum.com 1098 765432 1 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE This monograph provides a comprehensive overview of recent advances in the field of vasopressin and oxytocin. In the summer of 1997, scientists from over 20 countries congregated in Montreal for the 1997 World Congress of Neurohypophysial Hormones, a conference that united the fields of vasopressin, neurohypophysis and oxytocin in a single joint meeting that gave rise to the present book. The organization of a joint meeting was prompted by several recent developments. Specifically the molecular characterization of the vasopressin/oxytocin receptor family made it mandatory to adopt an integrated view and to discuss the vasopressin/oxytocin ligand/receptor family as a whole. To ensure em­ phasis on novelty, the conference focused on advances made over the last two years and also included important contributions by scientists that had not previously been associated with the vasopressin/oxytocin field. Vasopressin and oxytocin are two neurohormones that exert a wide spectrum of cen­ tral and peripheral actions. Accordingly, the vasopressin/oxytocin field embraces a large number of different domains, ranging from neuroscience, endocrinology, and oncology to renal, reproductive, and cardiovascular physiology and pathology. Highlights from these recent developments that are included in the present book include the following: * • Two gene ablation experiments ("knock-out mice") produced dramatic unex­ pected phenotypes: one resulting in total absence of the entire hypothalamo­ neurohypophysial system4 and the other in complete suppression of parturition in the presence of normal embryonic developmene9• A third gene ablation experi­ ment, the oxytocin "knock-out" mouse, provided insight into oxytocin's physi­ ological roles.30,3) • Important progress has been achieved in the area of oxytocin and vasopressin re­ ceptor function, including receptor structure/function analysis43-50, receptor-asso­ ciated signaling mechanisms32-35 , post-receptor effector systems5) ,52, and the regulation of receptor gene expression36--42 • Novel specific antagonists have been developed for the different receptor sub­ types with possible applications in fields ranging from cardiovascular pathophysi­ ology, congestive heart failure and hypertension to primary dysmenorrhea and premature labor53-jj), all areas of particular pharmacotherapeutic interest. Of note is the unexpected finding that the steroid progesterone itself has the capacity to * Numbers correspond to chapter numbers (see Index). v vi Preface Montevideo 1959 Aspen 1984 Lac Beauport 1984 Smuggler's Notch 1987 Montpellier 1990 Arlington 1991 Berlin 1993 Stade 1995 Figure 1. Historical "pedigree structure" of neurohypophysial hormone conferences. The authors wish to ac­ knowledge the important help Gf Dr. Maurice Manning, Toledo, USA , in compiling the data for the present figure. act as an oxytocin antagonist by binding directly to the oxytocin receptor and in­ hibiting its signaling functions36 . • The molecular mechanisms underlying cell-specific central and peripheral oxyto­ cin and vasopressin gene expression have been further elucidatied2-4.37. • Sophisticated biophysical and histochemical approaches have yielded insights into intrinsic membrane properties7-9 and synaptic inputs IO ,1 3.1 6.18. 19 that give rise to the characteristic and distinct firing patterns of vasopressin and oxytocin neurons. New in vitro approaches have shed light on the integrative functions of neurohy­ pophysial nerve terminals25. • New knowledge has been gained with respect to the physiology and the mecha­ nisms of action of centrally released neurohypophysial peptides5,6,2o.2 1.26-29, spe­ cifically with respect to the "autocontrol" ofmagnocellular neurons I8.19 . • The list of transmitter molecules modulating hypothalamic neuronal activity now includes amino acidslo.II.J4.15, steroid molecules acting via classical genomic and novel non-genomic mechanismsi3,J5, as well as gaseous transmitters such as nitric oxide23.24 . The 1997 World Conference was the offspring of a long-standing tradition of Neuro­ hypophysial Hormone Conferences. As illustrated in Fig. I , the historical "pedigree" of these meetings extends now over 42 years. The first international symposium was organ­ ized by Hans Heller in Bristol in 1956. This was a few years after the successful sequenc­ ing and synthesis of oxytocin and vasopressin by Du Vigneaud et al. and 60 years after the first report on vasopressor properties of posterior pituitary extracts by Oliver and ·Schafer. Thereafter, the tradition of specific Neurohypophysis Conferences was continued, but two additional "lineages" emerged, giving rise over the years to a series of separate Oxytocin and Vasopressin Conferences. Each of these meetings provided a stimulating forum for ex- Preface vii change of knowledge and forged lasting collaborations and friendships. Whereas the Nasu Meeting in 1995, under the expert guidance of Dr. T. Saito, joined the vasopressin and the neurohypophysis lineages into a "Joint World Congress", the 1997 World Congress in Montreal welcomed, in addition, oxytocin as an equal partner and thus attempted to re­ unite all three lineages. We hope that, as a result, the present book will provide a useful in­ tegrative reference volume for the specialized investigator and a stimulating textbook for interested students, clinicians and investigators from the vast number of fields that touch on the exciting area of neurohypophysial hormone research. Hans H. Zingg Charles W. Bourque Daniel G. Bichet ACKNOWLEDGMENTS We would like to thank the generous sponsors who made the 1997 World Congress of Neurohypophysial Hormones possible. Special thanks are due to the Canadian Centre for Clinical Research and Development, Wyeth-Ayerst Research, Canada, and Wyeth-Ay­ erst Research, USA; Ferring Pharmaceuticals, Sweden; Merck Research Laboratories,
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