RECENT ADVANCES IN TRYPTOPHAN RESEARCH Tryptophan and Serotonin Pathways ADV ANCES 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 Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 390 ANTIMICROBIAL RESISTANCE: A Crisis in Health Care Edited by Donald L. Jungkind, Joel E. Mortensen, Henry S. Fraimow, and Gary B. Calandra Volume 391 NATURAL TOXINS 2: Structure, Mechanism of Action, and Detection Edited by Bal Ram Singh and Anthony T. Tu Volume 392 FUMONISINS IN FOOD Edited by Lauren S. Jackson, Jonathan W. DeVries, and Lloyd B. Bullerman Volume 393 MODELING AND CONTROL OF VENTI LA TION Edited by Stephen J. G. Semple, Lewis Adams, and Brian J. Whipp Volume 394 ANTIVIRAL CHEMOTHERAPY 4: New Directions for Clinical Application and Research Edited by John Mills, Paul A. Volberding, and Lawrence Corey Volume 395 OXYTOCIN: Cellular and Molecular Approaches in Medicine and Research Edited by Richard Ivell and John A. Russell Volume 396 RECENT ADVANCES IN CELLULAR AND MOLECULAR ASPECTS OF ANGIOTENSIN RECEPTORS Edited by Mohan K. Raizada, M. Ian Phillips, and Colin Sumners Volume 397 NOVEL STRATEGIES IN THE DESIGN AND PRODUCTION OF VACCINES Edited by Sara Cohen and Avigdor Shafferman Volume 398 RECENT ADVANCES IN TRYPTOPHAN RESEARCH: Tryptophan and Serotonin Pathways Edited by Graziella Allegri Filippini, Carlo V. L. Costa, and Antonella Bertazzo A Continuation Order Plan is available for this series. A continuation order will bring delivery of eacb new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. RECENT ADVANCES IN TRYPTOPHAN RESEARCH Tryptophan and Serotonin Pathways Edited by Graziella Allegri Filippini Carlo V. L. Costa Antonella Bertazzo University of Pad ova Padova, Italy PLENUM PRESS • NEW YORK AND LONDON Ltbrarv of Congress Cataloging-In-Publication Data Reclnt advances In trvptop~.n r.s.arc~ Irvptop~,n and serolonln p't~w.vs I .dlt.d by Grazl,ll. ~Il.grl Filippini. Carlo V.L. Cost" Anlonetl. B,rtlllO. p. c •. --(~dvanclS In u perl.tntal ..d ICIOI and blologV , v, "" 'Proceldlngs of the EIghth lntern'tlon,l H"tlng on TrvPtoph,n Res,arch, held ~un' 25-29, 1995, In Padov., II.1V'--T.p. versa. ,"cjygn blOllogrlphlL.1 rafer,nelS and Indu. ISBN ·13: 978-1-4813-8026-9 I. TrvPtophan--Congr,sse,. 2. Serotonln--CongrlssI,. I. Filippini. Grnllll, Allagrl. II. COSII, Carlo V. L. Ill. Bertillo. Antonelli. IV. Intern.lloo.1 Heetlng on TrvPtophan Research (81h 1995 Padua, It.IV) V. Series. 1DN....H, 1. TrVPloph.n--congrusu. 2. S.rCtOOln--congrtsus. WI AD5S9 v.398 1996 I au 60 R294 19961 OP562. T7R"I3 1996 612' . 1l1675--dc20 ON...M1ct..C for Library of Congress 96-20315 'Ie Proceedings of the Eighth International Meeting on Tryptophan Research, held June 25 - 29, 1995, in Padova, Italy ISBN·I3: 978·1·4613·8026·9 e·ISBN·13: 978·1·4613·0381·7 DOl: 10.1007/978·1·4613·0381·7 0 1996 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1996 A Division of Plenum Publishing Corporation 233 Spring SUeet, New York, N. Y. 10013 t0987654321 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, retording, or otherwise, without written permission from the Publisher PREFACE Wide and fascinating is the field of research on tryptophan, a most versatile amino acid, transformed, as it is, in our organism into many biologically active substances. This volume contains the proceedings of the Eighth International Meeting on Tryptophan Research, held at the University of Padova, Padova, Italy, from June 25 to 29 1995, under the auspices of the University of Padova, National Research Council, Italian Chemical Society-Division of Pharmaceutical Sciences, Region ofthe Veneto and City of Padova. The meeting was held in Padova to commemorate Prof. Luigi Musajo twenty years after his death and the editors dedicate this book to him in recognition of his pioneering work in tryptophan metabolism. Prof. Osamu Hayaishi delivered the Musajo Memorial Award Lecture: Tryptophan oxygenase. and sleep. Figure I shows the ISTRY President Prof. Simon N. Young presenting the Musajo Memorial Medal to Prof. Hayaishi during the Opening Ceremony. Two hundred scientists from twenty two countries participated in the meeting. These proceedings contain 121 papers encompassing a variety of topics and disciplines. The plenary lectures dealt with links between tryptophan, serotonin and brain, and clinical implications of tryptophan biology. The other papers have been divided into nine specific chapters: I. Tryptophan and serotonin: neurobiology and neurochemistry, 2. Immunosys tern and tryptophan catabolism, 3. Kynurenines and derivatives, 4. Indole derivatives as antioxidants, 5. Metabolic and clinical aspects, 6. Enzymes in tryptophan degradation, 7. Tryptophan and eating behaviour and nutritional aspects, 8. Tryptophan in peptides and proteins, 9. Chemical and analytical aspects of tryptophan and related compounds. For few contributors who were unable to provide a manuscript, we reproduced the early abstracts. At the Conference Dinner the President of ISTRY gave Emeritus Professors R.R. Brown, G. Curzon, R. Kido a Medal Award to mark their outstanding contributions. The meeting was sponsored by: Universita degli Studi di Padova, Ministero Univer sita e Ricerca Scientifica e Tecnologica-Roma, Consiglio Nazionale delle Ricerche-Roma, Regione Veneto, Comune di Padova, Fondazione Cas sa di Risparmio Padova e Rovigo, Banca Popolare Veneta, Pharmacia-Milano, and Polifarma-Roma. We gratefully acknow ledge their support. We would also thank the University of Padova for providing excellent facilities for the Opening Ceremony, our colleagues of the programme committee and all who helped in the preparation of and during the meeting. Last but not least, we would like to express our gratitude to all participants, invited speakers and chairpersons, for the outstanding quality of their contributions to the success of the meeting. v vi Preface Figure 1. Prof. Simon N. Young, the President of ISTRY gives the Musajo Memorial Award Medal to Prof. Osamu Hayaishi. Finally, we wish to thank the Plenum Press, especially Mr. Robert Wheeler, Bertha O'Keefe, and Greg Safford, for their helpful cooperation. The next ISTRY Meeting will be organized by Dr. F. Artigas and will be held in Barcelona, Spain, in 1998. Graziella Allegri Filippini Carlo VL. Costa Antonella Bertazzo Padova, Italy, 1995 CONTENTS Opening Address by the President oflSTRY .................................. xvii MUSAJO MEMORIAL AWARD LECTURE 1. Tryptophan, Oxygenase, and Sleep 3 O. Hayaishi PLENARY LECTURES 2. Metabolism and Biology of Tryptophan: Some Clinical Implications. . . . . . . . .. 15 R. R. Brown 3. Brain Tryptophan: Normal and Disturbed Control ......................... 27 G. Curzon 4. Brain Serotonin, Carbohydrate-Craving, Obesity and Depression. . . . . . . . . . . .. 35 R. J. Wurtman and J. J. Wurtman TRYPTOPHAN AND SEROTONIN: NEUROBIOLOGY AND NEUROCHEMISTRY 5. The Effect of Low Brain Serotonin on Mood and Aggression in Humans: Influence of Baseline Mood and Genetic Factors ..................... 45 S. N. Young, R. O. Pihl, C. Benkelfat, R. Palmour, M. Ellenbogen, and D. Lemarquand 6. Adaptative Changes of the Serotonergic System after Antidepressant Treatments 51 F. Artigas, N. Bel, 1. M~ Casanovas, and L. Romero 7. The Effects of a Selective Inhibitor of Tryptophan 2,3-Dioxygenase and a Combined Inhibitor of Tryptophan 2,3 Dioxygenase and 5-HT Reuptake on Serotonergic Function in the Rat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 61 M. Salter, R. Hazelwood, C. 1. Pogson, R. Iyer, D. J. Madge. H. T. Jones, B. R. Cooper, R. F. Cox, C. M. Wang, and R. P. Wiard vii viii Contents 8. Effect of Valine on 5-HT Neurotransmission and Mood. . . . . . . . . . . . . . . . . . . .. 67 P. J Cowen, D. J. Williamson, and S. F. B. McTavish 9. Tryptophan and 5-HT in Psychiatric Illness .............................. 73 P. L. Delgado, A. J. Gelenberg, F. Moreno, C. Laukes, and L. Strayer 10. Tryptophan Metabolism and Disposition in Relation to Alcohol and Alcoholism 75 A. A.-B. Badawy 11. Endogenous Kynurenine Derivatives and Pain . . . . . . . . . . . . . . . . . . . . . . . . . . .. 83 J. Weil-Fugazza 12. Sexual Behavior in Male and Female Rats after a Tryptophan-Free Amino Acid Mixture ...................................................... 89 E. A. Moja and F. Benedetti 13. Delirium after Cardiac Surgery: The Possible Role of Tryptophan in Relation to the Other Neutral Aminoacids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 93 R. C. van der Mast, W. W. van den Broek, D. Fekkes, L. Pepplinkhuizen, and F. H. J. Roest 14. The Possible Role of Tryptophan in Migraine ............................ 97 S. Salmon, C. Curradi, E. Del Bene, and F. Sicuteri 15. Tryptophan and Epilepsy ............................................. 101 G. Lunardi, P. Mainardi, V. Rubino, M. Fracassi, F. Pioli, S. Cultrera, and C.Albano 16. Plasma Tryptophan Levels in Children with Epilepsy before and after Antiepileptic Treatment .......................................... 103 D. D. Milovanovic, H. L. Stevanovic, and N. Jovic 17. Plasma Tryptophan Levels in the Patients with Cervicobrachial and Lumbosacral Pain Syndromes ..................................... 107 D. D. Milovanovic, H. L. Stevanovic, and J. Pavlovic 18. Melatonin in Insomniac Patients and Effects of Sleep Medication ............ 113 A. Rodenbeck, G. Hajak, and G. Huether 19. Tyrosine and Tryptophan Derivatives in Pig Lumbar Cerebrospinal Fluid: Effects of Subc hronic Administration of Dopa Associated with Benzeraside ................................................... 119 S. Banting, G. Achilli, A. Banting, D. Le Bars, and J. Weil-Fugazza IMMUNOSYSTEM AND TRYPTOPHAN CATABOLISM 20. The Kynurenine Pathway and Neurologic Disease: Therapeutic Strategies ..... 125 M. P. Heyes 21. Increase of Tryptophan in Serum and in Cerebrospinal Fluid of Patients with HIV Infection during Zidovudine Therapy ........................... 131 D. Fuchs, M. Gisslen, M. Larsson, G. Norkrans, L. Hagberg, and H. Wachter Contents ix 22. Immunobiology ofPicolinic Acid ...................................... 135 G. Melillo, M. C. Bosco, T. Musso, and L. Varesio 23. Control of Extracellular Matrix Degradation by Interferon-y: The Tryptophan Connection .................................................... 143 J. Varga, T. Yufit, E. Hitraya, and R. R. Brown 24. Activated Cellular Immunity and Decreased Serum Tryptophan in Healthy Pregnancy .................................................... 149 D. Fuchs, H. Schrocksnadel, G. Baier-Bitterlich, O. Dapunt, and H. Wachter 25. Tryptophan Starvation is Involved in Human Interferon-Gamma Mediated Apoptosis ..................................................... 155 M. W. Taylor, V. K. Konan, and D. Yu 26. Cytokine and Drug Modulation of Kynurenine Pathway Metabolism by Blood Mononuclear Cells ............................................. 161 K. Saito, M. Seishima, A. Noma, S. P. Markey, and M. P. Heyes 27. Kynurenine Enzymatic Pathway in Human Monocytes-Macrophages: Effect of Interferon-y Activation .......................................... 167 R. G. Ferrario, S. Baratte, C. Speciale, and P. Salvati 28. Regulation of the Kynurenine Pathway by IFN-y in Murine Cloned Macrophages and Microglial Cells ................................. 171 D. Alberati-Giani, P. Ricciardi-Castagnoli, C. Kohler, and A. M. Cesura 29. The Effects ofInduced Kynurenine Pathway on Immunocytochemical Changes in Rat Tissues Following Excessive L-Tryptophan Consumption ......... 177 N. Ronen, B. Gross, D. Ben-Shachar, and E. Livne 30. Serum Tryptophan, Kynurenine, and Neopterin in Patients with Guillain-Barre-Syndrome (GBS) and Multiple Sclerosis (MS) ........... 183 V. Rudzite, J. Berzinsh, I. Grivane, D. Fuchs, G. Baier-Bitterlich, and H. Wachter KYNURENINES AND DERIVATIVES 31. K ynurenines and Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 1 I. P. Lapin 32. Basic Mechanisms of Kynurenine Actions in the Central Nervous System ...... 195 T. W. Stone, D. G. MacGregor, R. A. Smith, P. Jones, W. M. H. Behan, and D. I. Graham 33. Kynurenine Hydroxylase and Kynureninase Inhibitors as Tools to Study the Role of Kynurenine Metabolites in the Central Nervous System ......... 203 F. Moroni, R. Carpenedo, and A. Chiarugi 34. Kynurenine Metabolism in the Rat Brain in Vivo: Effect of Acute Excitotoxic Insults ........................................................ 211 R. Schwarcz, G. Ceresoli, and P. Guidetti x Contents 35. Kynurenic Acid-Enhancing and Anti-Ischemic Effects of the Potent Kynurenine 3-Hydroxylase Inhibitor FCE 28833 in Rodents ............ 221 C. Speciale, M. Cini, H.-Q. Wu, P. Salvati, R. Schwarcz, A. Molinari, M. Calabresi, and M. Varasi 36. Regulation of Quinolinic Acid in the Normal Rat Brain by Kynurenine Pathway Precursors ............................................. 229 J. Luthman, E. Viinerman, G. Fredriksson, and B. Fornstedt-Wallin 37. The Neurotoxin Quinolinic Acid Is Increased in Spinal Cords of Mice with Herpes Simplex Virus Encephalitis ................................ 241 J. F. Reinhard, Jr. and E. M. Flanagan 38. Quinolinic Acid and Active Oxygens: Possible Contribution of Active Oxygens during Cell Death in the Brain .................................... 247 K. Goda, R. Kishimoto, S. Shimizu, Y. Hamane, and M. Ueda 39. Kynurenine and Pteridines in Changes of Membrane Fluidity ................ 255 V Rudzite, E. Jurika, D. Fuchs, G. Baier-Bitterlich, and H. Wachter 40. The Kynurenines and the Seizures ...................................... 263 V I. Guzeva, I. B. Mikhailov, and N. V Melnikova 41. Systemic Administration of Kainate Induces Marked Increases of Endogenous Kynurenate in Various Brain Regions and Plasma of Rats .............. 265 H. Baran, M. Gramer, D. Honack, and W. Loscher 42. Effect of Route of Administration on the Metabolism of Quinolinic Acid-6~ in Animals .................................................... 267 L. V. Hankes and M. Schmaeler 43. Modulation of Extracellular Kynurenic Acid Content by Excitatory Amino Acids in Primary Cultures of Rat Astrocytes ......................... 273 L. Curatolo, C. Caccia, C. Speciale, L. Raimondi, M. Cini, M. Marconi, A. Molinari, and R. Schwarcz INDOLE DERIVATIVES AS ANTIOXIDANTS 44. Evolutionary Aspects of Indoleamines as Radical Scavengers: Presence and Photocatalytic Turnover of Indoleamines in a Unicell, Gonyaulax polyedra ...................................................... 279 R. Hardeland, G. Behrmann, B. Fuhrberg, B. Poeggeler, S. Burkhardt, H. Uria, and B. Obst 45. Utilization of Supero xide Anion by Indoleamine Oxygenase-Catalyzed Tryptophan and Indoleamine Oxidation ............................. 285 O. Hayaishi 46. Antioxidant Properties ofIndole-3-Pyruvic Acid .......................... 291 V Politi, S. D' Alessio, G. Di Stazio, and G. De Luca