VASOPRESSIN AND OXYTOCIN Molecular, Cellular, and Clinical Advances ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
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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, USA; Fujisawa Pharmaceutical Co. Ltd., Japan; Japan Tobacco Inc., Pharmaceutical Divi• sion; Sanofi Research, France. We thank all the colleagues world-wide who, via the In• ternet, helped to shape the Conference. This includes specifically the members of the Scientific Advisory Committee, Drs. M. Birnbaumer, J.P.H. Burbach, H. Gainer, C. In• gram, T. Insel, S. Ishikawa, R. Ivell, G. Leng, J.A. Russel, C.D. Sladek and J. Verbalis. For the organisation of the Conference, the McGill Conference Office was of invaluable help, specifically Ms. Charlotte Benabdallah, Coordinator, and Ms. Joan Gros, Manager. Fi• nally, we would like to extend our thanks to the staff from Plenum Press, including Ms. Maryann McCarra, Editor, for their patience and co-operation in the preparation of this volume.
ix CONTENTS
Historical Overview
I. Vasopressin Receptors: A Historical Survey Serge Jard
Biosynthesis of Vasopression and Oxytocin
2. Cell-Specific Gene Expression in Oxytocin and Vasopressin Magnocellular Neurons...... 15 Harold Gainer
3. Hypothalamic Transcription Factors and the Regulation of the Hypothalamo-Neurohypophysial System ...... 29 1. Peter H. Burbach, Hermien van Schaick, Sofia Lopes da Silva, Ceriel H. J. Asbreuk, and Marten P. Smidt
4. POU Domain Factors in Neural Development...... 39 Marcus D. Schonemann, Aimee K. Ryan, Linda Erkman, Robert J. McEvilly, John Bermingham, and Michael G. Rosenfeld
5. Local Protein Synthesis in Magnocellular Dendrites: Basic Elements and Their Response to Hyperosmotic Stimuli ...... 55 Dan Ma and John F. Morris
6. Vasopressin Gene Expression in Rat Choroid Plexus ...... 59 Adam Chodobski, Brian E. Wojcik, Y. Peng Loh, Kimberly A. Dodd, Joanna Szmydynger-Chodobska, Conrad E. Johanson, David M. Demers, Zachary G. Chun, and Nicolas P. Limthong
Neuronal Activity and Release
7. Electrophysiological Distinctions between Oxytocin and Vasopressin Neurons in the Supraoptic Nucleus ...... 67 William E. Armstrong and Javier E. Stem
xi xii Contents
8. Mechanisms of Neuroendocrine Cell Excitability 79 Glenn I. Hatton and Zhenhui Li
9. Properties of the Transient K+ Current in Acutely Isolated Supraoptic Neurons from Adult Rat ...... 97 Thomas E. Fisher and Charles W. Bourque
10. GabaB Receptors and Supraoptic Neuronal Activity 107 Q. 1. Pittman, D. Mouginot, and S. B. Kombian
11. Local Glutamatergic and Gabaergic Synaptic Circuits and Metabotropic Glutamate Receptors in the Hypothalamic Paraventricular and Supraoptic Nuclei ...... 117 Jeffrey G. Tasker, CherifBoudaba, and Laura A. Schrader
12. Progesterone Regulates Hypothalamic Oxytocin mRNA Levels through Gamma Aminobutyric Acid ...... 123 Abraham Thomas and Janet A. Amico
13. Differential Effects of the Neurosteroid Pregnenolone Sulphate on Oxytocin and Vasopressin Neurones in Vitro ...... 127 J. B. Wakerley and C. M. Richardson
14. Regulation of Vasopressin Release by Ionotropic Glutamate Receptor Agonists ...... 129 Delmore 1. Morsette, Kerry L. Swenson, Shenon E. Badre, and Celia D. Sladek
15. Role of N-Methyl-D-Aspartate (NMDA) Receptors in Vasopressin and Oxytocin Responses to Emotional Stimuli ...... 131 Kinji Yagi, Tatsushi Onaka, and Atsuko Yoshida
16. Eiectrophysiological Studies of Oxytocin Neurons in Organotypic Slice Cultures...... 135 P. Jourdain, B. Dupouy, R. Bonhomme, D. T. Theodosis, D. A. Poulain, and J. M. Israel
17. Inhibitory Actions ofNociceptin (Orphanin FQ) on Rat Supraoptic Nucleus Oxytocin and Vasopressin Neurones in Vitro...... 147 N. Doi, M. B. Dutia, C. H. Brown, G. Leng, and J. A. Russell
18. New Aspects of Firing Pattern Autocontrol in Oxytocin and Vasopressin Neurones ...... 153 F. Moos, L. Gouzenes, D. Brown, G. Dayanithi, N. Sabatier, L. Boissin, A. Rabie, and P. Richard
19. Intrahypothalamic Vasopressin Release: An Inhibitor of Systemic Vasopressin Secretion? ...... 163 M. Ludwig and G. Leng Contents xiii
20. Differential Central and Peripheral Release of Vasopressin and Oxytocin in Response to Swim Stress in Rats ...... 175 Mario Engelmann, Carsten T. Wotjak, and Rainer Landgraf
21. Pregnancy and Aging: Two Model Systems with Altered Release Patterns of Oxytocin and Vasopressin within the Hypothalamus ...... 179 Inga Neumann, Alexandra Wigger, Martin Hatzinger, and Martin E. Keck
22. Effect of Age and Testosterone on the Vasopressin Response to Dehydration in F344 BNF 1 Male Rats ...... 183 J. Catudioc-Vallero, 1. M. Sands, H. E. Sidorowicz, 1. D. Klein, and C. D. Sladek
23. Evidence for Nitric Oxide (NO) Actions throughout the Forebrain Osmoresponsive Circuit ...... 187 Simon M. Luckman
24. Gaseous Neurotransmitter Modulation of Vasopressin and Oxytocin Release 191 Mary L. Forsling and Ashley Grossman
25. Membrane Excitability in the Neurohypophysis ...... 193 Russell A. Wilke, Gerard P. Ahem, and Meyer B. Jackson
Effects
26. Vasopressin's Depolarizing Action on Neonatal Rat Spinal Lateral Hom Neurons May Involve Multiple Conductances ...... 201 M. Kolaj and L. P. Renaud
27. Vasopressin Action in the Mammalian Cerebral Cortex ...... 211 Roberta Diaz Brinton, Rose S. Yamazaki, Qi Chen, and Michael Son
28. Oxytocin, Vasopressin, and the Neuroendocrine Basis of Pair Bond Formation ...... 215 Thomas R. Insel, James T. Winslow, Zuoxin Wang, and Larry 1. Young
29. Central Oxytocin Neurotransmission: Receptor Characterisation and Role in Modulating Limbic Circuits in the Peripartum Period ...... 225 C. D. Ingram, M. G. Terenzi, H. C. Howard, and R. J. Windle
30. Targeted Reduction of Oxytocin Expression Provides Insights into Its Physiological Roles ...... 231 W. Scott Young III, Emily Shepard, A. Courtney DeVries, Andreas Zimmer, Mary E. LaMarca, Edward 1. Ginns, Janet Amico, Randy 1. Nelson, Lothar Hennighausen, and Kay-Uwe Wagner,
31. Phenotypic Expression of an Oxytocin Peptide Null Mutation in Mice ...... 241 James T. Winslow, Larry 1. Young, Elizabeth Hearn, Brenden Gingrich, Zouxin Wang, Qiuxia Guo, Martin M. Matzuk, and Thomas R. Insel xiv Contents
32. Antiproliferative Effect of Oxytocin through Specific Oxytocin Receptors in Human Neuroblastoma and Astrocytoma Cell Lines ...... 245 Paola Cassoni, Anna Sapino, Anna Stella, and Gianni Bussolati
33. Phosphorylation of Proteins Induced in a Murine Pre-T Cell Line by Neurohypophysial Peptides ...... 247 Henri Martens, Ouafae Kecha, Chantal Charlet-Renard, Marie-Paule Defresne, and Vincent Geenen
Signalling
34. Molecular Pharmacology of Human Vasopressin Receptors ...... 251 Marc Thibonnier, Doreen M. Conarty, Judith A. Preston, Pamela L. Wilkins, Liliana N. Berti-Mattera, and Rafael Mattera
35. Molecular Mechanisms Regulating the Effects of Oxytocin on Myometrial Intracellular Calcium ...... 277 Barbara M. Sanborn, Kimberly Dodge, Monju Monga, Ansha Qian, Wei Wang, and Caiping Yue
Receptors: Expression and Regulation
36. Genomic and Non-Genomic Mechanisms of Oxytocin Receptor Regulation. . .. 287 H. H. Zingg, E. Grazzini, C. Breton, A. Larcher, F. Rozen, C. Russo, G. Guillon, and B. Mouillac
37. The Molecular Basis of Oxytocin and Oxytocin Receptor Gene Expression in Reproductive Tissues ...... 297 Richard Ivell, Ross A. Bathgate, Norbert Walther, and Tadashi Kimura
38. Transcriptional Regulation of the Oxytocin Receptor Gene 307 Tracy L. Bale and Daniel M. Dorsa
39. Female Reproduction in Mice Lacking the Prostaglandin F Receptor: Roles of Prostaglandin and Oxytocin Receptors in Parturition ...... 317 Y. Sugimoto, E. Segi, K. Tsuboi, A. Ichikawa, and S. Narumiya
40. Expression of the Oxytocin Receptor and Oxytocin Gene in Human Oocytes and Pre implantation Embryos...... 323 Solveig Stock and Christina Osterlund
41. Vasopressin Regulates Adrenal Functions by Acting through Different • Vasopressin Receptor Subtypes ...... 325 E. Grazzini, G. Boccara, D. Joubert, M. Trueba, T. Durroux, G. Guillon, N. Gallo-Payet, L. Chouinard, M. D. Payet, and C. Serradeil Le Gal
42. All Three Vasopressin Receptor Sub-Types Are Expressed by Small-Cell Carcinoma...... 335 William G. North, Michael J. Fay, and Jinlin Du Contents xv
Receptors: Structure/Function
43. Processing and Ligand-Induced Modifications of the V2 Vasopressin Receptor ...... 339 Hamid M. Sadeghi, Giulio Innamorati, Evette Esqueda, and Mariel Bimbaumer
44. Molecular Aspects of Vasopressin Receptor Function ...... 347 Torsten Schoneberg, Evi Kostenis, Jie Liu, Thomas Gudermann, and Jiirgen Wess
45. Mapping Peptide Antagonist Binding Sites of the Human VIa and V2 Vasopressin Receptors...... 359 B. Mouillac, S. Phalipou, N. Cotte, M. N. Balestre, M. Hibert, M. Manning, and C. Barberis
46. Structure/Function Studies on Receptors for Vasopressin and Oxytocin 363 M. Wheatley, S. R. Hawtin, and N. J. Yarwood
47. Identification ofa Constitutively Active Mutant of the Human Oxytocin Receptor ...... 367 Bice Chini, Elena Albertazzi, Piero De Benedetti, and Francesca Fanelli
48. Identification of Neurohypophysial Hormone Receptor Domains Involved in Ligand Binding and G Protein Coupling ...... 371 RolfPostina, Elzbieta Kojro, and Falk Fahrenholz
49. Mutations in the Vasopressin V2 Receptor and Aquaporin-2 Genes in Twelve Families with Congenital Nephrogenic Diabetes Insipidus ...... 387 Rosa Vargas-Poussou, Lionel Forestier, Marie Dominique Dautzenberg, Patrick Niaudet, Michele Dechaux, and Corinne Antignac
50. Functional Study of Two V2 Vasopressin Mutant Receptors Related to NDI: P322S and P322H ...... 391 D. Morin, Y. Ala, N. Sabatier, N. Cotte, G. Hendy, R. Vargas, M. Dechaux, C. Antignac, M. Hibert, D. Bichet, and C. Barberis
Renal Actions of Va so pression
51. Studies of Renal Aquaporin-2 Expression during Renal Escape from Vasopressin-Induced Antidiuresis ...... 395 Joseph G. Verbalis, Takashi Murase, Carolyn A. Ecelbarger, S0ren Nielsen, and Mark A. Knepper
52. Prompt and Sustained Regulation of Aquaporin-2 by Arginine Vasopressin in Collecting Duct Cells and Clinical Implication of Urinary Excretion of Aquaporin-2 ...... 407 San-e Ishikawa, Takako Saito, Sei Sasaki, and Toshikazu Saito
53. Recent Advances in the Understanding of Water Metabolism in Heart Failure 415 R. W. Schrier and P. Y. Martin xvi Contents
Antagonists
54. Nonpeptide Antagonists for Vasopressin Receptors: Pharmacology of SR 121463A, A New Potent and Highly Selective Vz Receptor Antagonist...... 427 C. Serradeil-Le Gal
55. VPA-985, a Nonpeptide Orally Active and Selective Vasopressin Vz Receptor Antagonist ...... 439 Peter S. Chan, Joseph Coupet, Hyung C. Park, Fong Lai, Dale Hartupee, Peter Cervoni, John P. Dusza, Jay D. Albright, Xun Ru, Hossein Mazandarani, Tarak Tanikella, Cherrie Shepherd, Laura Ochalski, Trina Bailey, Tim Yeung Wai Lock, Xiaoping Ning, Joseph R. Taylor, and Walter Spinelli
56. Effects of Chronic AVP V2R Blockade in Congestive Heart Failure in Sheep: Comparison with Chronic ACE Inhibition ...... 445 Mareo Naitoh, John Power, Paddy A. Phillips, John Risvanis, Colin L Johnston, and Louise M. Burrell
57. Vasopressin Induces Opposite Changes in Blood Flow in the Skin and the Muscular Circulation ...... 447 Daniel Hayoz, Jiirg Hengstler, Bernard Noel, and Hans R. Brunner
58. Discovery of Novel Selective Hypotensive Vasopressin Peptides: A New Vasodilating Vasopressin Receptor? ...... 451 W. Y. Chan, Nga Ching Wo, Stoytcho Stoev, Ling Ling Cheng, and Maurice Manning
59. Safety, Tolerability, and Pharmacokinetics of SR 49059, a V 1a Vasopressin Receptor Antagonist, after Repeated Oral Administration in Healthy Volunteers ...... 455 R. Brouard, V. Laporte, C. Serradeil Le Gal, R. Pignol, H. Jang, F. Donat, G. Lockwood, D. Fournie, and F. Dreux
60. Evidence for an Involvement of Vasopressin in Mechanism of Primary Dysmenorrhea and Effect of the Non-Peptide Vasopressin VIa Receptor Antagonist, SR 49059, on the Uterus of Non-Pregnant Women ...... 467 M. Akerlund, T. Bossmar, R. Brouard, and M. Steinwall
61. Progress in the Development of Oxytocin Antagonists for Use in Preterm Labor ...... 473 Peter D. Williams, Mark G. Bock, Ben E. Evans, Roger M. Freidinger, and Douglas J. Pettibone
Index 481