Substance P and Neurokinins

1.L. Henry R. Couture A.C. Cuello G. Pelletier R. Quirion D. Regoli Editors and Neurokinins Proceedings of "Substance P and Neurokinins-Montreal '86" A Satellite Symposium of the XXX International Congress of The International Union of Physiological Sciences

With 198 illustrations

Springer-Verlag New York Berlin Heildelberg London Paris Tokyo Editors James L. Henry, Ph.D., Department of Physiology, McGill University, Montreal, Quebec, Canada H3G I Y6 Rejean Couture, Ph.D., Department of Physiology, University of Montreal, c.P. 6208, Montreal, Quebec, Canada H3C 3T8 A. Claudio Cuello, M.D., Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G IY6

Georges Pelletier, Ph.D., MRC Group in Molecular Endocrinology, Centre Hospitalier de L'Universite, Laval, Quebec, Canada GIV 4G2 Remi Quirion, Ph.D., Douglas Hospital Research Centre and Department of Psychiatry, McGill University, Verdun, Quebec, Canada H4H IR3

Domenico Regoli, M.D., Department of Pharmacology, Medical School, University of Sherbrooke, Sherbrooke, Quebec, Canada JlH 5N4

LCCN 87-16669

© 1987 Springer-Verlag New York Inc. Softcover reprint of the hardcover 1st edition 1987 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer-Verlag, 175 Fifth Avenue, New York, New York 10010, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use of general descriptive names, trade names, trademarks, etc. in this publication, even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act. may accordingly be used freely by anyone. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

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ISBN-13: 978-1-4612-9\09-1 e-ISBN-13: 978-1-4612-4672-5 DOl: 10.1007/978-1-4612-4672-5 Preface

Sarajevo was the site of the first international meeting on substance P. It was held in 1961, thirty years after the first report of the discovery of substance P by Von Euler and Gaddum. The proceedings which follow are from a symposium held twenty-five years after the first meeting. These twenty-five years have seen a vast expansion in this field ofresearch. This family of now includes a number of different mammalian and non-mammalian related peptides. Beyond the early physiological and pharmacological studies, there is important new information coming from the full spectrum of disciplines in the basic medical sciences, including molecular biology, which has given us important insights into the biosynthetic mechanisms of origin of these peptides. Montreal was chosen as the site for the 1986 meeting. The name given to it was "Sub• stance P & Neurokinins-Montreal '86." This name was modelled after the one held in Dublin in 1982, but neurokinins were added to acknowledge the broader family of peptides. The meeting was held as a Satellite Symposium of the XXX International Congress of the International Union of Physiological Sciences in Vancouver. The venue was McGill University, and the dates were 21-23 July, 1986. This symposium was particularly important for North Americans because it was the first international meeting on substance P to take place on this continent. The previous meeting in this field was held in Maidstone, U.K., in 1984, as a Satellite Symposium of the International Congress of Pharmacology. The next meeting is scheduled for 1988 in Graz, Austria. The purpose of the 1986 meeting was to bring together those involved in research on the neurokinins for an update on developments in the area. For the proceedings, the format of an extended abstract was chosen to increase the novelty of the material presented without the extensive commitment from the authors required by a longer manuscript. It was the success of a related formula from the meeting in Dublin which prompted this decision. In terms of the meeting itself, attempts were made to encourage younger scientists to participate. Emphasis was placed in the program on volunteer presentations. Subsidies were given out to those for whom such assistance could make a difference in being able to attend. This was made possible by generous donations from the following:

McGill University Ministere de l'Enseignement superieur de Fonds de la recherche en sante du Quebec la Science et de la Technologie Medical Research Council of Canada Universite Laval vi

Air Canada Amersham Corp., U.S.A. Canadian Pacific Airlines Astra AB, Sweden Fidia S.P.A. E. Merck GMBH, Germany Council for Tobacco Research, U.S.A. CIBA-Geigy Ltd., Canada CIBA-Geigy Corp., U.S.A. Du Pont, NEN Research Products, Canada Proctor & Gamble Co., U.S.A. Merck Frosst Canada Inc Institut Armand-Frappier, Laval, Quebec Glaxo Group Research Ltd, U.K. Universite de Montreal CIDEM, City of Montreal Universite de Sherbrooke Miles Laboratories Inc., U. S. A. Ferring Arzneimittel GMBH, Germany Abbott Laboratories, U.S.A. Novabiochem AG, Switzerland Nova Pharmaceutical Corp., U.S.A. Ferring Pharmaceuticals, Sweden Bachem Feinchemikaliem AG, Switzerland Warner-Lambert Co, U.S.A. Bristol-Myers Co., U.S.A. Pfizer Inc., U.S.A. Sandoz Canada Inc. Protein Research Foundation, Japan Bio-Mega Inc., Canada McNeil Pharmaceuticals, U.S .A. Stuart Pharmaceuticals, U.S.A. Merrell Dow Pharmaceuticals, U.S.A. Bachem Inc., U.S.A. Norwich Eaton Pharmaceuticals Medicorp Inc., Canada and Inc., U.S.A. Allied Fisher Scientific, Canada.

James L. Henry McGill University Contents

Discussions of Nomenclature for Tachykinins and Tachykinin Receptors 1. L. Henry ...... xvii

PART I. SYNTHESIS; METABOLISM; MOLECULAR BIOLOGY; NEW NEUROKININS S. E. Leeman

1. Substance P and Neurokinins S. E. Leeman ......

2. Cloning and Expression of Rat and Human Tachykinin Genes T. I. Bonner, A. C. Young, and H.-U. Affolter...... 3

3. Structure, Expression and Regulation of the Rat Preprotachykinin I Gene 1. E. Krause, M. S. Carter, Z. S. Xu, and M. R. MacDonald ...... 5

4. Striatonigral Tachykinin Biosynthesis I. Effect of the Dopamine Antagonist Haloperidol M. 1. Bannon, 1.-M. Lee, P. Giraud, A. C. Young, H.-U. Affolter, and T. I. Bonner ...... 8

5. Thyroid Hormone Regulates Tachykinin Gene Expression in Rat Anterior Pituitary J. A. Jonassen, D. Mullikin-Kilpatrick, and S. E. Leeman ...... 12

6. Phylogeny of the Tachykinins J. M. Conlon, C. F. Deacon, M. Thorndyke, L. Thim, and S. Falkmer ...... 15

7. Metabolism of Tachykinins by Cell-Surface Peptidases A. J. Turner and N. M. Hooper ...... 18 VIJI

8. Structure and Post-Translational Processing of the Preprotachykinins A. 1. Harmar, A. R. Pierotti, A. Armstrong, K. Chapman, 1. S. Chahl, 1. Going, C. R. W Edwards, R. Rosie, and 1. Pascali.... 21

9. Substance P Content in and Capsaicin-Evoked Release from Dissociated Cultures of Rat Nodose Ganglion (Vagal Sensory) Neurons D. B. MacLean and M. F. Wheeler ...... 24

10. Biosynthesis of Substance P and in the Enteric Nervous System C. F. Deacon and 1. M. Conlon...... 27

II. Striatonigral Tachykinin Biosynthesis p. 1. Elliott, A. Young, H.-U. Affolter, T. I. Bonner, and M. 1. Bannon...... 30

12. Substance P Precursor Studies in Carcinoid Tumours N. Corbally, D. Powell, and K. Tipton...... 33

13. Chronic Neuroleptic Administration Reduces Striatal Substance P mRNA and the Localization of Substance P mRNA in Rat Brain by In Situ Hybridization 1. A. Angulo, L. G. Davis, B. A. Burkhart, and G. R. Christoph .... 37

PART II. BINDING ASSAYS AND CONFORMATIONAL STUDIES L. L. Iversen

14. Multiple Receptors and Binding Sites for Tachykinins L. L. Iversen, A. C. Foster, K. 1. Watling, A. T. McKnight, B. 1. Williams, and C. M. Lee ...... 40

15. Multiple Tachykinin Binding Sites in Rat Brain and Peripheral Tissues C. M. Lee, N. 1. Campbell, B. 1. Williams, and L. L. Iversen...... 44

16. 3H-Neurokinin Band [1251]_Bolton Hunter Eledoison Label Identical Tachykinin Binding Sites in the Rat Brain L. Bergstrom, Y. Torrens, M. Saffroy, 1. C. Beaujouan, S. Lavielle, G. Chassaing, 1. L. Morgat, 1. Glowinski, and A. Marquet ...... 47

17. Characterization of Tachykinin Receptor Subtypes Using Selective Ligands R. Laufer, E. Rubini, C. Gilon, M. Chorev, and Z. Selinger...... 50

18. Characterization of Binding of [1251] lodohistidyl-Substance K to Tachykinin K-Sites in Hamster Bladder S. H. Buck ...... 52

19. Endothelial-Dependent Binding of e251]-Bolton- Hunter Substance P in Blood Vessels 1. A. Stephenson, R. 1. Summers, and E. Burcher ...... 53 ix

20. Tachykinin-Induced Phosphatidylinositol Turnover in Hamster Urinary Bladder K. J. Watling, N. Suman-Chauhan, and D. R. Bristow...... 56

21. Conformationally Restricted Analogues of Substance P O. Ploux, S. Lavielle, G. Chassaing, S. Julien, A. Marquet, J .-c. Beaujouan, Y. Torrens, L. Bergstrom, and J. Glowinski 60

22. Toward the Bioactive Conformation of Tachykinins? G. Chassaing, O. Convert, S. Lavielle, and O. Ploux 63

23. Evidence for the Zipper Model in Tachykinin Receptor Binding G. C. Landis, B. S. Wire, T. F. Burks, D. L. Kreulen, and V. J. Hruby ...... 66

24. Effects of Substance P on the Binding of Ligands to Nicotinic Acetylcholine Receptors on Torpedo Electroplaque Membranes S. M. Simasko and G. A. Weiland...... 69

25. Interaction of Analgesic Capsaicin Analogs with Substance P Receptors D. G. Payan, and L. M. Brand ...... 72

26. Tachykinins and Phosphatidyl Inositol Turnover in Rat Brain T. V. Dam, E. Escher, and R. Quirion...... 75

27. Tyr8 -Substance P Binding Study on a Plasma Membrane from Dog Ileum Smooth Muscle M. J. Muller, H. Sato, andE. E. Daniel...... 78

28. Multiple Tachykinin Binding Sites in Hamster, Guinea-Pig and Rat Bladder E. Burcher and S. H. Buck...... 80

29. Tachykinin P-type Binding Sites in Dog Kidney R. J. Summers, J. A. Stephenson, and E. Burcher 81

30. Substance P Binding Sites in Guinea-Pig Enteric Ganglia J. C. Bornstein and E. Burcher...... 84

31. Autoradiographic Localization of Substance P Binding Sites in Guinea-Pig Respiratory Tract D. J. Watkins and E. Burcher...... 87

32. [12sIl-Bolton Hunter Substance P Specific Binding Sites on Cortical Astrocytes from New Born Mouse in Primary Culture Y. Torrens, J. C. Beaujouan, M. Saffroy, D. de Montety, L. Bergstrom, and J. Glowinski ...... 90

33. Autoradiographic Distribution of Binding Sites for Iodinated Tachykinins in the Rat Central Nervous System T. L. O'Donohue, C. J. Helke, E. Burcher, C. W Shults, and S. H. Buck ...... 93 x

34. Neurokinin Receptors in Human Brain R. Quirion, H. Mount, T. V. Dam, P. Boksa, S. Buck, E. Burcher, and T. L. O'Donohue ...... 96

PART III. BIOLOGICAL ASSAYS; T ACHYKININ ANTAGONISTS D. Regoli

35. Receptors for Neurokinins in Peripheral Organs D. Regoli, G. Drapeau, S. Dion, and P. D' Orleans-Juste 99

36. Substance-P-Induced Desensitization in Canine Cephalic Arteries is not Mimicked by Substance K, , or M. A. Moskowitz, C. Kuo, S. E. Leeman, and M. Jessen...... 108

37. Multiple Neurokinin Receptors in the Rat Lower Urinary Tract C.A. Maggi, P. Santicioli, L. Abelli, S. Giulliani, M. Furio, M. Parlani, and A. Meli ...... III

38. Structure-Activity Relationships of Neurokinin A and B E. Munekata, F. Osakada, H. Tanaka, and K. Kubo ...... 114

39. Tachykinin Antagonists with Cyclic Structures E. Escher, P. D'OrIeans-Juste, S. Dion, and D. Regoli 116

40. Electrical and Mechanical Responses of Vascular Muscle to Tachykinis G. Haeusler, and J.-E. de Peyer ...... 119

41. [D-Pro2 , D_Trp6.8, Nle lO] -: Pharmacological Profile of a Novel Neurokinin Antagonist J. L. Vaught, R. Scott, D. Wright, and H. Jacoby ...... 122

42. Isolated Arterial and Venous Vessels as Selective Pharmacological Preparations for Neurokinins P. D'Orieans-Juste, S. Dion, N. E. Rhaleb, G. Drapeau, and D. Regoli ...... 125

43. Neurokinin Fragments and Analogues as Selective Activators of Receptors S. Dion, P. D'Orleans-Juste, N. E. Rhaleb, G. Drapeau, P. Rovero, and D. Regoli ...... 129

44. Mammalian Neurokinins: Structure-Activity Study of the N- and C-Terminals G. Drapeau, P. Rovero, P. D'Orleans-Juste, S. Dion, N. E. Rhaleb, and D. Regoli ...... 132

45. Neurokinin Receptor Mechanisms in Smooth Muscle J. M. Hall, and I. K. M. Morton ...... 135

46. Neurokinin Receptors in Guinea Pig Intestinal Muscle I. K. M. Morton and J. M. Hall ...... 138

47. Multiple Neurokinin Receptors in the Guinea Pig Ileum H. I. Jacoby, I. Lopez, D. Wright, and J. L. Vaught ...... 141 xi

48. Synthesis and Biological Activity of Agonists for the Neuronal Tachykinin Receptor in Guinea Pig Ileum D. Ron, R. Laufer, J. Frey, C. Gilon, Z. Selinger, and M. Chorev ...... 144

49. Tachykinin Activation of Muscarinic Inhibition in Canine Small Intestine is Substance P in Nature J. E. T. Fox, T. J. McDonald, L. Alford, and F. Kostolanska .... 146

50. Evidence for Three Distinct Peripheral Neurokinin Receptors Using a Putative Neurokinin B Antagonist C. W. Murray, A. Cowan, D. L. Wright, J. L. Vaught, and H.I. Jacoby ...... 149

51. Identification and Localization of Substance P Receptors on the Endothelium of the Pig Coronary Artery N. Gulati, H. Huggel, R. Mathison, D. Regoli, and J.-L. Beny .. 152

52. Activity of the C-Terminal Part in Tachykinins on Guinea Pig Ileum and Trachea Preparations R. Michelot, M. Mayer, S. Magneney, J. Thierry, and P. Potier 158

53. Relative Vasodilatory Potencies of Substance P, Deca-Substance P. and Nona-Substance P in the Canine Forelimb D. E. Dobbins, M.J. Buehn, and J. M. Dabney ...... 161

54. Hemodynamic Actions of Substance P in Anesthetized Rats J. C. Hancock ...... 164

55. The Effect of Substance P Antiserum on Responses of Guinea-Pig Isolated Ileum to Substance P and Acetylcholine L. A. Chahl, and C. A. Thornton ...... 166

56. Antibodies as Tools for Studying Tachykinins and Their Receptors J. Y. Couraud, Y. Frobert, D. Renzi, P. Lamourette, J. Grassi, M. Conrath, D. Regoli, and P. Pradelles ...... 168

57. Characterization of Spinal Actions of Ten Substance P Analogs R. Couture, A. Gupta, R. Kerouac, E. Escher, and D. Regoli .... 17l

58. Substance P Antagonists and Analgesia: Do They or Don't They? J. L. Vaught, R. Scott, and H. I. Jacoby ...... 176

59. Substance P in Human Spermatozoa and Modulation of Sperm Motility by Substance P and Its Antagonists B. V. Rama Sastry, and V.E. Janson ...... 179

PART IV. DISTRIBUTION AND ROLE IN PERIPHERAL TISSUES A. C. Cuello

60. Effector Roles of Substance P in Peripheral Branches of Sensory Neurons A. C. Cuello ...... 182

61. Tachykinins and Gastrointestinal Propulsion in the Rat In Vivo P Holzer, U. Holzer-Petsche, and S. Leander ...... 187 xii

62. Substance P Effects on the Long-Term Regulation of Adrenal Catecholamine Levels P. Boksa ...... 189

63. Effects of Substance P and Gene-Related on Skeletal Muscle Microcirculation A. Ohlen, L. Lindbom, T. H6kfelt, P. Hedqvist, and W. Staines 192

64. Substance P Effect on the Secretory Process in Rat Parotid Gland C. Dreux, V. Imhoff, P. Maoduit, and B. Rossignol ...... 195

65. Effects of Substance P on Blood Flow of the Dental Pulp in Dogs S. Kim, and 1. Dorscher-Kim ...... 197

66. Influence of Anesthesia and Atropine on Plasma Extravasation Induced by Mammalian Tachykinins in the Rat R. Kerouac, and R. Couture ...... 200

67. Tachykinin-Induced Plasma Extravasation in Rat Skin is Mediated Through the SP-P Receptor P. V. Andrews, and R. D. Helme ...... 203

68. Peptides as Promoters of Paracellular Permeability: A Novel Role For Tachykinins? P.K. Rangachari, and D. McWade ...... 205

69. Release of Substance P from Isolated Guinea Pig Heart D. B. Hoover ...... 208

70. Effects of Tachykinins on the Rat Stomach In Vivo and In Vitro U. Holzer-Petsche, H. Seitz, and F. Lembeck ...... 210

71. Endoluminal Substance P is Released by a Meal A. Ferrara, S. R. Money, and B. M. Jaffe ...... 212

72. Effect of Substance P and Neurokinins on the Endocrine Secretion of the Pancreas and Stomach Y. N. Kwok ...... 214

73. Development of the Substance P-Like Immunoreactive Innervation of the Mesenteric Vascular Bed in Normotensive and Hypertensive Rats T. M. Scott, J. Robinson, and J. Foote ...... 217

74. Increase of Plasma Substance P- and Neurokinin A-Like Immunoreactivity During Carcinoid Flushing P. Geppetti, D. Renzi, D. Caleri. C. Nediani, G. Vannozzi, A. Morettini, and M. Fanciullacci ...... 220

75. HPLC and Immunohistochemical Characterization of Substance P-Like Immunoreactivity in a Human Pheochromocytoma M. G. Spillantini, E. Baldi, S. Frilli, S. Marabini, M. Mannelli, F. Amenta, and P. Geppetti ...... 223 Xlii

76. Role of Capsaicin-Sensitive Primary Afferent Nerves in the Neuroendocrine Copulation Reflex H. H. Traurig, R. E. Papka, and M. E. Rush ...... 226

77. Substance K-, Substance P-, and Calcitonin Gene-Related Peptide-Immunorective Nerves in Female Reproductive Organs R. E. Papka, and H. H. Traurig ...... 229

78. Substance P- and -Like Immunoreactivity in Maternal and in Umbilical Cord Plasma and in Amniotic Fluid M. Di Tommaso, G.c. Di Renzo, E. Cosmi, D. Renzi, C. Nediani, M.G. Spillantini, S. Michelacci, and P. Geppetti .... 232

PART V. ROLES ASSOCIATED WITH SENSORY NEURONS M. Otsuka

79. Effects of Spantide on Reflexes of Slow Time Courses in Isolated Rat Spinal Cord M. Otsuka and M. Yanagisawa ...... 235

80. A Depressant Action of Substance P on Spinal Nociceptive Neurons in the Rat and Cat R. W. Ryall and A. J. Pini ...... 239

81. Physalaemin, Substance P and Neurokinin A Potentiate Purine-Induced Depression of Spinal Dorsal Horn Neurones in the Cat M. W. Salter and J. L. Henry ...... 241

82. Multiple Tachykinins and Calcitonin Gene-Related Peptide (CGRP) in Capsaicin-Sensitive Nerves of Sympathetic Ganglia A. Saria, R. C. Ma, E. Theodorsson-Norheim, J. M. Lundberg, G. Skofitsch, R. Amann, and N. J. Dun ...... 244

83. Intrathecal Substance P Produces a Long-Term Inhibition of the Spinal Analgesic Effect of Noradrenaline J. Sawynok and P. W. Nance ...... 246

84. Pharmacological Modulation of Antidromic Vasodilatation Measured by Laser Doppler Flowmetry R. Gamse and A. Saria ...... 249

85. Capsaicin Sensitive Afferent Neurons Involved in Neuroendocrine Regulations F. Lembeck and R. Amann ...... 25 I

86. Sensory C Fiber Mediate Mucociliary Responses to Airway Irritants S. Lindberg ...... 254

87. Substance P Modulates Cholinergic Regulation of the Nicotinic Acetylcholine Receptor of PC 12 Cells N. D. Boyd and S. E. Leeman ...... 257 xiv

88. Evidence of ACTH-Adrenal and Chronic Stress-Induced Down Regulation of Substance P in the Sensory Vagus Nerve D. B. MacLean, J. C. Eldridge, and A. Brodish ...... 260

89. Substance P and Hypoxic Excitation of the Carotid Body N. R. Prabhakar, J. Mitra, H. Lagercrantz, C. von Euler, and N. S. Chemiack ...... 263

90. Immunochemical Studies on Substance P Release from Muscularis Mucosa of Opossum Esophagus E. E. Daniel, M. Nagahma, H. Sato, J. Jury, and P. Bowker .... 266

91. Substance P-Immunoreactive Fibers in the Trigeminal Sensory Nuclei of Pit Vipers, Trimeresurus Flavoviridis S.-i. Terashima ...... 270

92. Miotic Effect of Echothiophate Iodide in Humans: Possible Role of Iris Substance P M. Fanciullacci, M. Nicolodi, U. Pietrini, P. Geppetti, S. Rizzo, and F. Sicuteri ...... 273

93. The Effects of Neurokinin A and Calcitonin Gene-Related Peptide on Mucociliary Activity S. Lindberg, J. DoIta, and U. Mercke ...... 276

94. Neurokinin A Excites Nociceptive and Non-Nociceptive Dorsal Hom Neurones in the Cat Spinal Cord J. L. Henry and M. W. Salter ...... 279

95. Modality Specific Analgesia Produced by Intrathecal Anti-Sub• stance P Antibody P. W. Nance, J. Sawynok, and D. M. Nance ...... 282

96. A Quantitative Study of Substance P and Coexistence in Primary Afferent Axonal Varicosities in the Rat Spinal Cord M. M. Tuchscherer, and V. S. Seybold ...... 285

97. Sciatic Nerve Stimulation and Substance P Release from Posterior Pituitary Lobe (PPL) in Rats U. Szkudlarek, J. Mazanowska-Gajdowicz, D. Cannon, and W. Z. Traczyk ...... 288

98. Neurokinin A as a Transmitter of Primary Afferents Involved in Thermal Nociception S. M. Fleetwood-Walker, R. Mitchell, P. J. Hope, N. EI-Yassir, and V. Molony ...... 291

VI. DISTRIBUTION AND ROLES IN THE CENTRAL NERVOUS SYSTEM T. Hokfelt

99. Reflections on Substance P and Some Related Peptides T. Hokfelt and G. Ju ...... 294 xv

100. Regional Distribution of Neurokinin A and Substance P in the Rat Central Nervous System Y. Takano, A. Nagashima, Y. Hataa, H. Masui, and H. Kamiya 297

101. Regulation of Substance P Immunoreactivity in GAB A Neurons of Monkey Visual Cortex by Sensory Deprivation E. G. Jones, S. H. C. Hendry, and J. DeFelipe ...... 300

102. Interactions Between Substance P and Nicotinic Acetylcholine Receptors in Pain Control Mechanisms in the Rat J. Del Rio, M. C. De Felipe, and M. T. Molinero ...... 302

103. Central Modulation of Blood Pressure by N- and C-Terminal Fragments of Substance P J. M. Stewart, F. Miley, and M. E. Hall ...... 305

104. Effects of Tachykinins on Dopamine Release in the Striatum: In Vitro and In Vivo Studies P. Baruch, F. Petit, F. Artaud, L. Basbeits, G. Godeheu, A. Cheramy, and J. Glowinski ...... 308

105. Immunocytochemical Localization of Substance P-Like Immunoreactivity in the Human Hypothalamus G. Pelletier ...... 311

106. Substance P and Somatostatin-Like Immunoreactivities in Synaptic Glomeruli of the Rat Substantia GeIatinosa, as Revealed by Bi• Specific Monoclonal Antibodies A. Ribeiro-da-Silva, and A. C. Cuello ...... 313

107. A Sex Difference in the Pattern of Substance P-Like Immunoreactivity in the Bed Nucleus of the Stria Terminalis C. W. Malsbury, and K. McKay ...... 318

108. Suppression of Noradrenaline-Induced Ovulation by Administration of Substance P into the Third Cerebral Ventricle in Pseudo-Pregnant Rats E. Potargowicz, and W. Z. Traczyk ...... 321

109. Spinal Actions of Substance P on Cardiovascular Responses in the Rat D. Huberdeau, R. Kerouac, A. Gupta, and R. Couture ...... 324

110. Evidence for at Least Two Tachykinin Receptor Subtypes in the Mammalian Spinal Cord M. Wienrich, I. Lues, B. E. B. Sandberg, and J. Harting ...... 328

III. Spinal and Supraspinal Substance P Antinociception: Synergistic Interaction R. E. Rodriguez, and F. D. Rodriguez ...... 331

112. Substance P Empty Neuron: A Conceptualization of Organic and Functional Deafferentation Syndromes F. Sicuteri, M. Nicolodi, and M.G. Spillantini ...... 334 xvi

113. Excitatory Effects of Substance P and Related Peptides on -Sensitive Non-Pyramidal Neurones in Rat Hippocampus M. Raggenbass, J. -Po Wuarin, and J.J. Dreifuss ...... 337

114. Electrophysiological Correlates of and Other in Developing Rat Cerebral Cortex S.K. Sharma ...... 340

115. Effects of an Amino-Terminal Fragment of Substance P on Brain Dopamine and Serotonin Metabolism M. E. Hall, P. DeArmey, and J. M. Stewart ...... 344

116. Effect of Carbamazepine on Substance P Content in the Rat Brain H. Mitsushio, M. Takashima, and M. Torn ...... 347

117. Release of Substance P, Acetylcholine and Methionine from Mouse Cerebral Slices: Effects of Nicotine O. S. Tayeb, and B. V. Rama Sastry ...... 350

118. Different Functional Roles for Substance P and in the Striato-Nigral Pathways of the Rat M. Herrera-Marschitz, I. Nylander, M. Reid, M. T. Sharp, T. H6kfelt, L. Terenius, and U. Ungerstedt ...... 353

119. Striato-Nigral Tachykinin Neurons and Influence from Striatal Dopamine and GABA N. Lindefors, E. Brodin, U. Tossman, and U. Ungerstedt ...... 356

120. Substance P, Thyrotropin-Releasing Hormone, and Serotonin Neurons Sprout in Cervical Ventral Horn of the Wobbler Mouse, a Model for Motoneuron Disease L. L. Vacca-Galloway, C. Steinberger, E. Poole, and C. D. Menon ...... 359

121. Intra-Raphe Substance P5-11 but Not Muscimol-Induced Hyperactivity is Mediated by Serotonin Neurons J. M. Paris, and S. A. Lorens ...... 363

122. Heterogeneity of Central and Peripheral Tachykinin Binding Sites P. W. Mantyh, C. R. Mantyh, and J. E. Maggio ...... 366

123. Research on Tachykinins: Clinical Trends B. Pernow ...... 372

124. A Network of Defense F. Lembeck ...... 380

Index ...... 389 Discussions of Nomenclature for Tachykinins and Tachykinin Receptors 1. L. Henry

Department of Physiology, McGill University, Montreal, Canada H3G 1Y6

During the IUPS Satellite Symposium The outcome of the discussion on "Substance P and Neurokinins - Montreal nomenclature for tachykinin receptors was '86" nomenclature for tachykinins and for the following: tachykinin receptors was discussed in two sessions set aside for this purpose. SP-P receptor defined by Lee & The first such session was a joint Iversen (1982) meeting of the Scientific Advisory NK-P (Regoli et al., 1985) committee and the Local Organizing NK-A SP-E (Lee & Iversen, 1982) committee, and was held the evening of 22 SP-K (Buck et al., 1984) July, 1986. Those present were Drs. SP-E (Laufer et al., 1985) Joaquin Del Rio, Jacques Glowinski, Leslie NK-A (Regoli et al., 1985) L. Iversen, Christo fer C. Jordan, chi-Ming Lee, Susan E. Leeman, Fred Lembeck, NK-B SP-E (Buck et al., 1984) Masanori Otsuka, Bengt Pernow, Sune Rosell SP-N (Laufer et al., 1985) and John M. Stewart, from the Scientific NK-B (Regoli et al., 1985) Organizing Committee, and Drs. Rejean couture, Claudio Cuello, James L. Henry, Georges Pelletier, Remi Quirion and Citations for these references are as Domenico Regoli, from the Local Organizing follows: Committee. Drs. Maurice Manning, Jose M. Musacchio and Michael A. Moskowitz were Buck,S.H., E.Burcher, C.W.Shults, also invited to attend. This meeting was W. Lovenberg & T. L. 0' Donohue Novel chaired by Professor F. Lembeck. pharmacology of substance K-binding The outcome of the discussion on si tes: a third type of tachykinin nomenclature for the tachykinins was a receptor. Science 226: 987-989, confirmation of support for the 1984. nomenclature suggested at the IUPHAR Satellite symposium "Substance P: Laufer,R., U.Warmser, Z.Y.Friedman, Metabolism and Biological Actions" which C.Gilon, M.Chorev & Z.Selinger took place in August, 1984. At that Neurokinin B is a preferred agonist meeting the following was recommended: for a neuronal substance preceptor and its action is antagonized by SP Substance P enkephalin. Proc. Nat. Acad. Sci. ELE USA 82: 7444-7448, 1985. PHY Physalaemin KAS Kassinin Lee,C.M., L.L.Iversen, M.R.Hanley, & UPE Uperolein B.E.B.Sandberg The possible ERP Eledoisin-related peptide existence of multiple receptors for NKA Neurok~nin A (= neurokinin substance P. NS Arch. Pharmacol. alpha), also known as 318: 281-287, 1982. neuromedin L or substance K NKB Neurokinin B (= neurokinin Regoli,D., p.D'Orleans-Juste, beta), also known as G.Drapeau, s.Dion & E.Escher neuromedin K Pharmacological characterization of TK Tachykinins as a group defined sUbstance P antagonists. In: by the c-terminal Hakanson,R. & F.Sundler, (eds) Tachykinin Antagonists, Elsevier Sci. Publ., Amsterdam, 1985. The second session devoted to nomenclature was held on 23 July, and was open to all participants at this Symposium who were interested in discussing the issue. This session was chaired by Professor B. Pernolll. After a period of discussion a vote was taken on the nomenclature for the mammalian tachykinins which confirmed support for the nomenclature recommended at the 1984 meeting. A more lengthy discussion ensued on the nomenclature for mammalian tachykinin receptors. By vote the following nomenclature was agreed upon: TK-l SP-P receptor defined above TK-2 = NK-A receptor defined above TK-3 = NK-B receptor defined above Once this vote had been taken it was pointed out that this nomenclature was already present in the literature for non-mammalian tachykinins. Later the same afternoon with all those present NK was approved as the appropriate sUbstitute for TK. Thus, the nomenclature would be: NK-l SP-P receptor defined above NK-2 NK-A receptor defined above NK-3 NK-B receptor defined above