ADVANCES IN PROSTAGLANDIN,LEUKOTRIENE, AND OTHERBIOACTIVE LIPID RESEARCH

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY

Editorial Board :

NATHAN BACK, State University of New York at Buffalo

IRUN R. COHE N, The Weivnann Institute of Science

DAVID KRITCHEVSKY, Wistar Institute

ABEL LAJTHA , N. S. Kline Institute fo r Psychiatric Research

RODOLFO PAOLETTI, University of Milan

Recent Volumes in this Series

Volume 517DOPAMINERGIC NEURON TRANSPLANTATION IN THE WEAVER MOUSEMODEL OF PARKINSON'S DISEASE

Edited by Lazaros C. Triarhou

Volume 518ADVANCES IN MALE MEDIATED DEVELOPMENTAL TOXICITY

Edited by Bernard Robaire and Barbara F. Hales

Volume 519POLYMER DRUGS IN THE CLINICAL STAGE: Advantages and Prospects

Edited by Hiroshi Maeda, Alexander Kabanov, Kazurori Kataoka, and Teruo Okano

Volume 520CYTOKINES AND AUTOIMMUNE DISEASE

Edited by Pere Santamaria

Volume 521IMMUNE MECHANISMS IN PAIN AND ANALGESIA

Edited by Halina Machelska and Christoph Stein

Volume 522NOVEL ANGIOGENIC MECHANISMS : Role of Circulating Progenitor Endothelial CelIs

Edited by Nicanor I. Moldovan

Volume 523ADVANCES IN MODELLING AND CLINICAL APPLICATION OF INTRAVENOUSANAESTHESIA

Edited by Jaap Vuyk and Stefan Schraag

Volume 524DIPEPTIDYL AMINOPEPTIDASES IN HEALTH AND DISEASE

Edited by Martin Hildebrandt, Burghard F. Klapp, Torsten Hoffmann,and Hans-Ulrich Demuth

Volume 525ADVANCES IN PROSTAGLANDIN , LEUKOTRIENE, AND OTHER BIOACTIVELIPID RESEARCH: Basic Science and Clinical Applications

Edited by Zeliha YazICI, Giancarlo Folco, Jeffrey M. Drazen, Santosh Nigam,and Takao Shimizu

A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volumeimmediately upon publication. Volumes are billed only upon actual shipment. For further information please contactthe publisher.

ADVANCES IN PROSTAGLANDIN, LEUKOTRIENE, AND OTHER BIOACTIVE LIPID RESEARCH Basic Science and Clinical Applications

Edited by

Zeliha YaZlCl University of Istanbul Istanbul, Turkey

Giancarlo C. Folco University of Milan Mi/an, Italy

Jeffrey M. Drazen Harvard Medical School Boston, Massachusetts

Santosh Nigam Free University of Berlin Berlin, Germany

and

Takao Shimizu University of Tokyo Tokyo, Japan

Springer Science+Business Media, LLC

Proceedings of the 12th International Conference on Advances in Prostaglandin. Leukotriene. and OIher Bioactive Lipid Rescarch: Basic Science and Clinical App[ications. held August 25- 29, 2002, in Istanbul, Turkey

ISSN 0065·2598

Q 2003 Springer Sciencc+l3usincss Media Ncw York OrigÎnally pub[ishcd by K[uwer I [>[enum Pub[ishers, New York În 2003 Softeover reprint of the hardeollcr 1 st cdition 2003

Ali rights reserved

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ISBN 978-1-4613-4831-3 ISBN 978-1-4419-9194-2 (eBook)DOI 10.1007/978-1-4419-9194-2

Contributors

Nader G. Abraham, Professor of Pharmacology, New York Medical, College,Valhalla, NY 10595, USA.

Kate Ackerman, Pulmonary and Critical Care Medicine, Brigham and Women'sHospital, 75Francis Street, Boston, MA 02115, USA.

Eyup S. Akarsu, Ankara University, Faculty of Medicine, Department ofPharmacology and Clinical Pharmacology, Sihhiye 06100 Ankara, Turkey .

Sibel Arat, Ankara University, Faculty of Medicine, Department of Pharmacologyand Clinical Pharmacology, Sihhiye 06100 Ankara, Turkey .

Hitoshi Arita, Shionogi Research Laboratories, Shionogi & Co., Ltd. 5-12-4 Sagisu,Fukushima-ku, Osaka 553-0002, Japan .

David M. Aronoff, Divisions of Infectious Diseases & Pulmonary/Critical CareMedicine, 6301 MSRB III, 1500 W. Medical Center Drive, Ann Arbor, MI48109­0642, USA.

Vicente Arroyo, Liver Unit, Hospital Clinic, Institut d'Investigacions BiomediquesAugust Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona 08036, Spain.

Michael Balazy, New York Medical College, Department of Pharmacology,Valhalla, NY 10595, USA.

Gene H. Barnett, Brain Tumor Institute/S80, Cleveland Clinic Foundation, 9500Euclid Avenue, Cleveland, OH 44195, USA.

v

vi CONTRIBUTORS

Ingrid Beck-Speier, GSF-National Research Center for Environment and HealthInstitute for Inhalation Biology, Ingolstaedter Landstr. 1, D-85764Neuherberg/Munich, Germany.

Sylvie G. Bernier, Research Center, Sainte-Justine Hospital, 3175 Cote Sainte­Catherine, Montreal, Quebec, H3T lC5, Canada.

Ghassan Bkaily, Departments of Pediatrics and Cell Biology, Universite deSherbrooke, 300112111 North Avenue, Fleurimont, Quebec, JIH 5N4, CANADA

Stephanie Blaie, INSERM U 348, Hopital Lariboisiere, 75475 Paris cedex 10,France.

Andreas M. Boehmler, University of Tiibingen, Department ofMedicine II Otfried­Miiller-Str. 10, 72076 Tiibingen, Germany.

Anna Bonanno, Istituto di Fisiopatologia Respiratoria, Centro Nazionale delleRicerche, Via U. La Malfa, 90146 Palermo, Italy.

Judy Bondar, Brain Tumor Institute/ND4-52A, Cleveland Clinic Foundation, 9500Euclid Avenue, Cleveland, OH 44195, USA.

Giovanni Bonsignore, Istituto di Medicina Generale e Pneumologia, Universita diPalermo, Via Trabucco 180,90146 Palermo, Italy.

Annie Bourdeau, Montreal Heart Institute, 5000 Belanger St., Montreal, Quebec,HIT lC8, CANADA

Olivier Boutaud, Division ofClinical Pharmacology, 514 RRB, 23rd Ave @ Pierce,Vanderbilt University, Nashville, TN, 37232-6602, USA.

Charles Brink, Xavier Norel and Laurence Walch, CNRS FRE 2536 HopitalBroussais, 96 rue Didot, 75014 Paris, France .

Christine M. Briton-Jones, Department of Obstetrics & Gynaecology, ChineseUniversity ofHong Kong, Hong Kong SAR.

Eva Burkert, Institute ofPharmaceutical Chemistry, University ofFrankfurt, Marie­Curie-Str. 9, D-60439 Frankfurt, Germany.

Jorge H. Capdevila, Department ofMedicine, Vanderbilt University Medical School,Medical Center North S-3223, Nashville, TN 37232, USA.

Maria F. Capparelli, Department of Pharmacology, New York Medical College,Valhalla, New York 10595, USA.

Chiara Carnini, Department ofPharmacological Sciences, University ofMilan, viaBalzaretti 9, Milan 20133, Italy.

CONTRIBUTORS vii

Mairead A Carroll, Department of Pharmacology, New York Medical College,Valhalla, New York 10595, USA.

Dan Chelarescu, Univ. Med. Pharm. "Gr. T. Popa", Universitatii 16, Iasi 6600,Romania.

Sylvain Chemtob , Research Center, Sainte-Justine Hospital, 3175 Cote Sainte­Catherine, Montreal, Quebec, H3T 1C5, Canada.

Monica K. Cheng, Department of Pharmacology, New York Medical College,Valhalla, New York 10595, USA.

Sanaa Choufani, Departments of Pediatrics and Cell Biology, Universite deSherbrooke, 300112lh North Avenue, Fleurimont, Quebec, JIH 5N4, Canada.

Joan Claria, DNA Unit, Hospital Clinic, Institut d'Investigacions BiomediquesAugust Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona 08036, Spain.

Flavio Coceani, Scuola Superiore Sant'Anna and Institute of Clinical PhysiologyCNR, Piazza Martiri della Liberta' 33, 56127 Pisa, Italy.

Florian Cocu, Chemical Pharmaceutical Research Institute, 112 Vitan Avenue,74373 Bucuresti 3, Romania.

Gabriela Constantin, Department of Pathology, University of Verona, Strada LeGrazie 8, Verona 37134, Italy.

Jean-Luc Cracowski , Laboratoire de Pharmacologie, Faculte de medecine deGrenoble, 38706 La Tronche Cedex, France.

Niru Dayal, GSF-National Research Center for Environment and Health Institutefor Inhalation Biology, Ingolstaedter Landstr. 1, D-85764 Neuherberg/Munich,Germany.

Marco De Curtis, Istituto Neurologico Besta, via Celoria, Milan 20133, Italy.

Claudio Denzlinger, Marienhospital Stuttgart, Department ofInternal Medicine, IIIBiiheimstr. 37, 70199 Stuttgart, Germany.

George T. De Sanctis, Pulmonary and Critical Care Medicine, Brigham andWomen's Hospital, 75 Francis Street, Boston, MA 02115, USA.

Pallavi R. Devchand, Ctr. for Experimental Therapeutics and Reperjusion Injury,Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

David Dishart, Department of Medical Biochemistry and Biophysics, Division ofPhysiological Chemistry II Karolinska Institutet, S-171 77 Stockholm, Sweden.

Vlll CONTRIBUTORS

Dan A. Dixon, Vanderbilt University, School ofMedicine, Department ofSurgery,Nashville, USA

Anabel B. Doumad, Department of Pharmacology, New York Medical College,Valhalla, New York 10595, USA.

Jeffrey M. Drazen, Harvard Medical School, Pulmonary and Critical Care Division,Department ofMedicine, 75 Francis Street, Boston, Massachusetts 02115, USA.

Michael W. Dunn, Department of Ophthalmology, New York Medical, College,Valhalla, NY 10595, USA.

Po-Hien Ear. Department of Biochemistry and Molecular Biology, Merck FrosstCanada, 16711, autoroute Transcanadienne, Kirkland, Quebec, H9H 3L1, Canada.

Joan Claria Enrich, Hospital Clinic, Villarroel I Ztl, 08036 Barcelona, Spain.

Bruno A Escalante, Centro de Investigacion y de Estudios Avanzados del InstitutoPolitecnico Nacional, Mexico DF 07300.

Jean-Pierre Falgueyret, Department ofBiochemistry and Molecular Biology, MerckFrosst Canada, 16711, autoroute Transcanadienne, Kirkland, Quebec, H9H 3L1,Canada.

L Fan, Research Center, Sainte-Justine Hospital, 3175 Cote Sainte-Catherine ,Montreal, Quebec, H3T 1C5, Canada.

Nicholas R Ferreri, Department of Pharmacology, New York Medical College,Valhal/a, New York 10595, USA.

Janos G. Filep, Research Center, Maisonneuve-Rosemont Hospital, 5415 boul. del 'Assomption, Montreal, Quebec, HIT 2M4, Canada.

Lutz Fischer, Institute ofPharmaceutical Chemistry, University ofFrankfurt, Marie­Curie-Str. 9, D-60439 Frankfurt, Germany.

Giancarlo Folco, Department ofPharmacological Sciences, University ofMilan, viaBalzaretti 9, Milan 20133, Italy.

Carole Gallet, INSERM U 348, Hdpital Lariboisiere, 75475 Paris cedex 10, France.

Ben Galper, Department ofRespiratory and Critical Care Medicine, Brigham andWomen's, Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 0211,USA.

Jean-Pierre Gascard, Centre Chirurgical Marie-Lannelongue, 133 av de laResistance, 92350 Le Plessis Robinson, France

CONTRIBUTORS ix

Femand Gobeil jr. , Research Center, Sainte-Justine Hospital, 3175 Cote Sainte­Catherine, Montreal, Quebec, H3T 1C5, Canada.

Mladen Golubic, Brain Tumor Institute, Cleveland Clinic Foundation, 9500 EuclidAvenue, Cleveland, OH 44195, USA.

Aida Habib, INSERM U 348, Hopital Lariboisiere, 75475 Paris cedex 10,France and the American University ofBeirut, Department ofBiochemistry, POBox11-236, Beirut, Lebanon.

Kohji Hanasaki, Shionogi Research Laboratories, Shionogi & Co., Ltd. 5-12-4Sagisu, Fukushima-ku, Osaka 553-0002, Japan

Christopher 1. Haines, Department of Obstetrics & Gynaecology, ChineseUniversity ofHong Kong, Hong Kong SAR.

Joseph A. Hankin, National Jewish Medical and Research Center, 1400 JacksonStreet, 80206 Denver, CO, USA.

Buaijiaer Hasimu, Second Internal Medicine, Nihon University School ofMedicine,Ooyaguchi-kamimachi, 30-1, Itabashi-ku, Tokyo 173-8610, Japan .

Hiroaki Hattori, Research Department, R&D Center, BML Inc., Saitama 350-1101,Japan .

Peter M. Henson, National Jewish Medical and Research Center, 1400 JacksonStreet, 80206 Denver, CO, USA.

Joachim Heyder, GSF-National Research Center for Environment and HealthInstitute for Inhalation Biology, Ingolstaedter Landstr. 1, D-85764Neuherberg/Munich, Germany.

Burkhard Hinz, Department of Experimental and Clinical Pharmacology andToxicology, Friedrich Alexander University Erlangen-Nuremberg, Fahrstrasse 17,D-91054 Erlangen, Germany.

Vijaykumar Holla. Department ofMedicine, Vanderbilt University Medical School,Medical Center North S-3209, Nashville, TN 37232, USA.

Chris Hong, Department ofRespiratory and Critical Care Medicine, Brigham andWomen's, Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115,USA.

Hiroyasu Inoue, Department of Pharmacology, National Cardiovascular, CenterResearch Institute, 5-7-1 Fujishiro-dai Suita, Osaka 565-8565, Japan .

x CONTRIBUTORS

E Israel, Department of Respiratory and Critical Care Medicine, Brigham andWomen's, Hospital, Harvard Medical School, 75Francis Street, Boston, MA, 02115,USA.

Tadao Iwasaki, Research Department, R&D Center, BML Inc., Saitama 350-1101,Japan.

Houli Jiang, Department of Pharmacology, New York Medical College, Valhalla,New York 10595, USA.

Wladimiro Jimenez, Hormonal Laboratory, Hospital Clinic, Institutd'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat deBarcelona, Barcelona 08036, Spain.

Mitsuo Jisaka, Department ofLife Science and Biotechnology, Shimane University,Matsue, Shimane 690-8504, Japan.

Emily C. Jones, 115 Henning Building, Department of Veterinary Science, ThePennsylvania State University, University Park, PA 16802, USA.

Jean-Sebastien Joyal, Research Center, Sainte-Justine Hospital, 3175 Cote Sainte­Catherine, Montreal, Quebec, H3T 1C5, Canada.

Maria Juhas, Division of Experimental Pathology, Department of LaboratoryMedicine, Lund University, Malmo University Hospital, entrance 78,fl. 3, 205 02Malmo, Sweden.

Katsuo Kanmatsuse, Second Internal Medicine, Nihon University School ofMedicine, Ooyaguchi-kamimachi, 30-1, Itabashi-ku, Tokyo 173-8610, Japan.

Lothar Kanz, University of Tiibingen, Department of Medicine IL (Hematology,Oncology, Immunology, Rheumatology), Otfried-Miiller-Str. 10, 72076 Tiibingen,Germany.

Orner Kalayci, Hacettepe University School of Medicine, Pediatric Allergy andAsthma Unit, Hacettepe, 06100 Ankara, Turkey.

Erwin Karg, GSF-National Research Center for Environment and Health Institutefor Inhalation Biology, Ingolstaedter Landstr. 1, D-85764 Neuherberg/Munich,Germany.

Eugene Kim, Ctr. for Experimental Therapeutics and Reperfusion Injury, Brighamand Women~ Hospital, 75Francis Street, Boston, MA 02115, USA.

Yoshihiro Kita, Department of Biochemistry and Molecular Biology, Faculty ofMedicine, The University ofTokyo, CREST ofJST, Tokyo 113-0033, Japan.

CONTRIBUTORS xi

Alane T. Koki, Phannacia Research and Development, St Louis, Missouri, MO63167, USA.

Miron Krimsky, Department of Biochemistry, Hebrew University-HadassahMedical, School, 91120 Jerusalem, Israel.

Ichiro Kudo , Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555,Japan.

Shinichiro Kokubun, Division of Receptor Biology, Advanced Medical ResearchCenter, Nihon University School of Medicine, Ooyaguchi-kamimachi, 30-1,Itabashi-ku, Tokyo 173-8610, Japan.

Tammy G. LeRiche, Department of Biochemistry and Molecular Biology, MerckFrosst Canada, 16711, autoroute Transcanadienne, Kirkland, Quebec, H9H 3LJ,Canada.

Bruce D. Levy, Pulmonary and Critical Care Medicine, Brigham and Women'sHospital, 75 Francis Street, Boston, MA 02115, USA.

Sylviane Levy-Toledano, INSERM U 348, Hopital Lariboisiere, 75475 Paris cedex10, France.

Andrew Liken, 115 Henning Building, Department of Veterinary Science, ThePennsylvania State University, University Park, PA 16802, USA

Craig M Lilly, Department ofRespiratory and Critical Care Medicine, Brigham andWomen's, Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115USA.

Michal Laniado-Schwartzman, Department of Pharmacology, New York, MedicalCollege, Valhalla, NY 10595, USA.

Marta Lopez-Parra, DNA Unit, Hospital Clinic, Institut d 'InvestigacionsBiomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona08036, Spain.

Shan Lu, Department of Life Science and Biotechnology, Shimane University,Matsue, Shimane 690-8504, Japan.

Konrad L. Maier, GSF-National Research Center for Environment and HealthInstitute for Inhalation Biology, Ingolstaedter Landstr. 1, D-85764Neuherberg/Munich, Germany.

Soner Mamuk, Ankara University, Faculty of Medicine, Department ofPharmacology and Clinical Pharmacology, Sihhiye 06100 Ankara, Turkey.

xii CONTRIBUTORS

Joseph A. Mancini, Department of Biochemistry and Molecular Biology, MerckFrosst Canada, 16711 , autoroute Transcanadienne, Kirkland, Quebec, H9H 3L1,Canada.

Lawrence 1. Mamett, Vanderbilt Institute ofChemical Biology, 850A RRB, 23rd Ave@ Pierce, Vanderbilt University, Nashville, TN, 37232-0146, USA.

A. Marilise Marrache, Research Center, Sainte-Justine Hospital, 3175 Cote Sainte­Catherine, Montreal, Quebec, H3T 1C5, Canada .

Jaime L. Masferrer, Pharmacia Research and Development, St Louis, Missouri, MO63167, USA.

Ramin Massoumi, Division ofExperimental Pathology, Department ofLaboratoryMedicine, Lund University, Malmo University Hospital, entrance 78,fl. 3, 205 02Malmo, Sweden

John C McGiff, Department of Pharmacology, New York Medical College,Valhalla, New York 10595, USA.

Angela Mirabella, Istituto di Medicina Generale e Pneumologia, Universita diPalermo, Via Trabucco 180,90146 Palermo, Italy.

Yoshikazu Miwa, Department of Clinical Pharmacology, Graduate School ofMedical Sciences, Kyushu University, Fukuoka, Japan.

Megumi Miyagi, Department of Clinical Pharmacology, Graduate School ofMedical Sciences, Kyushu University, Fukuoka, Japan.

Asami Morioka, Department of Life Science and Biotechnology, ShimaneUniversity, Matsue, Shimane 690-8504, Japan.

Jason D Morrow, Department of Pharmacology, Vanderbilt University School ofMedicine, 442 Robinson Research Building, Nashville, TN 37232-6600, USA.

Robert Mahle, University of Tiibingen, Department of Medicine IL (Hematology,Oncology, Immunology, Rheumatology), Otfried-Miiller-Str. 10, 72076 Tiibingen,Germany.

Martin 1. Mueller, Julius-von-Sachs-Institut fuer Biowissenschaften,Pharmazeutische Biologie, Julius-von-Sachs-Platz 2, 97082 Wuerzburg, Germany.

Makoto Murakami, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142­8555, Japan.

Robert C. Murphy , National Jewish Medical and Research Center, 1400 JacksonStreet, 80206 Denver, CO, USA.

CONTRIBUTORS xiii

Tsutomu Nagaya, Department of Life Science and Biotechnology, ShimaneUniversity, Matsue, Shimane 690-8504, Japan.

Tomohiro Nakayama, Division of Receptor Biology, Advanced Medical ResearchCenter, Nihon University School of Medicine, Ooyaguchi-kamimachi, 30-1,Itabashi-ku, Tokyo 173-8610, Japan.

Kiyoshi Nakagawa, Department ofMedicine, Vanderbilt University Medical School,Medical Center North S-3209, Nashville, TN 37232, USA.

Shoo Narumiya, Department of Pharmacology, Kyoto University Faculty ofMedicine, Yoshida, Sakyo-ku, Kyoto 606-8315, Japan.

Mihai Nechifor, Dept. Pharmacology, Univ. Med. Pharm. "Gr. T. Popa",Universitatii 16, Iasi 6600, Romania.

Adriana Negro, Univ. Med. Pharm. "Gr. T. Popa", Universitatii 16, Iasi 6600,Romania.

Christian K Nielsen, Division ofExperimental Pathology, Department ofLaboratoryMedicine, Lund University, Malmo University Hospital, entrance 78, fl. 3, 205 02Malmo, Sweden.

Kohji Nishimura, Department of Life Science and Biotechnology, ShimaneUniversity, Matsue, Shimane 690-8504, Japan.

Xavier Norel, CNRS FRE 2536 Hopital Broussais, 96 rue Didot, 75014 Paris,France.

John A. Oates, Division ofClinical Pharmacology, Vanderbilt University School ofMedicine, The Vanderbilt-Ingram Cancer Center, 691 Preston Building, Nashville,TN 37232-6838, USA.

Anthony Oguogho, Department of Nuclear Medicine, University of Vienna,Wiihringer Giirtel 18-20, 1090 Vienna, Austria.John Fredrik Ohd, Division ofExperimental Pathology, Department ofLaboratoryMedicine, Lund University, Malmo University Hospital, entrance 78, fl. 3, 205 02Malmo, Sweden.

Masa-atsu Ohya, Department of Life Science and Biotechnology, ShimaneUniversity, Matsue, Shimane 690-8504, Japan.

Rafal Olszanecki, Jagiellonian University, Medical College, Pharmacology,Cracow, Poland.

Marc Ouellet, Department of Biochemistry and Molecular Biology, Merck FrosstCanada, 16711, autoroute Transcanadienne, Kirkland, Quebec, H9H 3Ll, Canada.

xiv CONTRIBUTORS

Adebayo O. Oyekan, College of Pharmacy & Health Sciences, Texas SouthernUniversity, Houston, Texas 77004, USA.

Barbara Palumbo, Department of Nuclear Medicine, Universita degli Studi,Policlinio Monteluce, Via Brunamonti, 06100 Perugia, Italy.

Sailaja Paruchuri, Division of Experimental Pathology. Department of LaboratoryMedicine, Lund University. Malmo University Hospital, entrance 78, fl. 3, 205 02Malmo, Sweden.

Alessandra Paterno, Istituto di Fisiopatologia Respiratoria, Centro, Nazionale delleRicerche, Via U. La Malfa, 90146 Palermo, Italy.

Ally Pen, Department of Biochemistry and Molecular Biology, Merck FrosstCanada. 16711, autoroute Transcanadienne, Kirkland. Quebec. H9H 3L1, Canada .

M. David Percival, Department of Biochemistry and Molecular Biology, MerckFrosst Canada, 16711, autoroute Transcanadienne, Kirkland, Quebec, H9H 3L1,Canada.

Heidemarie Pilz, Department of Internal Medicine, Kaiserin-Elisabeth Hospital,Huglgasse 1-3, 1152 Vienna, Austria.

Anna Planaguma, DNA Unit, Hospital Clinic, Institut d 'Investigacions BiomediquesAugust Pi i Sunyer (IDIBAPS) , Universitat de Barcelona, Barcelona 08036, Spain .

Sandeep Prabhu, 115 Henning Building, Department of Veterinary Science, ThePennsylvania State University, University Park, PA 16802, USA

Richard A. Prayson, Department of Anatomic PathologylL25, Cleveland ClinicFoundation, 9500 Euclid Avenue. Cleveland, OH 44195, USA.

Mirella Profita, Istituto di Fisiopatologia Respiratoria, Centro Nazionale delleRicerche, Via U. La Malfa , 90146 Palermo, Italy.

Olof Radmark, Department of Medical Biochemistry and Biophysics, Division ofPhysiological Chemistry II Karolinska Institutet, S-171 77 Stockholm, Sweden.

Channa Reddy 115 Henning Building, Department of Veterinary Science, ThePennsylvania State University, University Park, PA 16802, USA.

Padala V. Reddy, 115 Henning Building, Department of Veterinary Science, ThePennsylvania State University, University Park, PA 16802, USA.

Alfredo Ribeiro-da-Silva, Department of Pharmacology and Therapeutics, McGillUniversity, McIntyre Medical Sciences Building. 3655 Promenade Sir-William­Osler, Montreal, Quebec, H3G 1Y6, Canada.

CONTRIBUTORS xv

Loredana Riccobono, Istituto di Fisiopatologia Respiratoria, Centro Nazionaledelle Ricerche, Via U. La Ma/fa, 90146 Palermo, Italy.

Denis Riendeau, Department ofBiochemistry and Molecular Biology, Merck FrosstCanada, 16711, autoroute Transcanadienne, Kirkland, Quebec, H9H 3U, Canada.

Francisca Rivera, Hormonal Laboratory, Hospital Clinic, Institut d'InvestigacionsBiomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona08036, Spain.

Joan Rodes, Liver Unit, Hospital Clinic, Institut d'Investigacions BiomediquesAugust Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona 08036, Spain.

Michael S. Rogers, Department ofObstetrics & Gynaecology, Chinese University ofHong Kong, Hong Kong SAR.

Marek Rola-Pleszczynski, Departments ofPediatrics and Cell Biology, Universitede Sherbrooke, 3001 J2lh North Avenue, Fleurimont, Quebec, JIH 5N4, Canada.

Barbara Rossi, Department ofPathology, University of Verona, Strada Le Grazie 8,Verona 37134, Italy.

Angelo Sala, Dipartimento di Scienze Famacologiche and Center forCardiopulmonary Pharmacology, Universita di Milano, 20133 Milan, Italy.

Bengt Samuelsson, Department ofMedical Biochemistry and Biophysics, DivisionofPhysiological Chemistry II Karolinska Institutet, S-171 77 Stockholm, Sweden.

Toshiyuki Sasaguri, Department of Clinical Pharmacology, Graduate School ofMedical Sciences, Kyushu University, Fukuoka, Japan.

Hitoshi Sawaoka, Vanderbilt University, School of Medicine, Department ofPharmacology, Nashville, USA.

Birgitta Schmidt, Ctr. for Experimental Therapeutics and Reperfusion Injury,Brigham and Women's Hospital, 75Francis Street, Boston, MA 02JJ5, USA..

Holger Schulz, GSF-National Research Center for Environment and Health Institutefor Inhalation Biology, Ingolstaedter Landstr. 1, D-85764 Neuherberg/Munich,Germany.

Gabriele Schumann, GSF-National Research Center for Environment and HealthInstitute for Inhalation Biology, Ingolstaedter Landstr. 1, D-85764Neuherberg/Munich, Germany.

Ouri Schwob, Department ofBiochemistry, Hebrew University-Hadassah Medical,School, 91120 Jerusalem, Israel.

XVI CONTRIBUTORS

Charles N. Serhan, Ctr. for Experimental Therapeutics and Reperfusion Injury,Brigham and Women's Hospital, 75Francis Street, Boston, MA 02115, USA..

Takao Shimizu, Professor and Chairman, Department of Biochemistry andMolecular Biology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku,Hongo, Tokyo 113-0033, Japan.

Liboria Siena, Istituto di Fisiopatologia Respiratoria, Centro Nazionale delleRicerche, Via U. La Malfa, 90146 Palermo, Italy.Helmut Sinzinger, Wi/helm Auerswald Atherosclerosis Research Group A-1090Vienna, Austria.

Martin G. Sirois, Montreal Heart Institute, 5000 Belanger St., Montreal, Quebec,H1T 1C8, Canada.

Anita Sjolander, Division of Experimental Pathology, Department of LaboratoryMedicine, Lund University, Malmo University Hospital, entrance 78, fl. 3, 205 02Malmo, Sweden .

Masayoshi Soma, Second Internal Medicine, Nihon University School ofMedicine,Ooyaguchi-kamimachi, 30-1, Itabashi-ku, Tokyo 173-8610, Japan .

Angela M. Bentes Souza, Department of Obstetrics & Gynaecology, ChineseUniversity ofHong Kong, Hong Kong SAR.

lana Stankova, Departments of Pediatrics and Cell Biology, Universite deSherbrooke, 3001 12th North Avenue, Fleurimont, Quebec, JiH 5N4, Canada.

Dieter Steinhilber, Institute ofPharmaceutical Chemistry, University ofFrankfurt,Marie-Curie-Str. 9, D-60439 Frankfurt, Germany.

Dagmar Szellas, Institute of Pharmaceutical Chemistry, University of Frankfurt,Marie-Curie-Str. 9, D-60439 Frankfurt, Germany.

Wojciech Szezcklik, Ctr. for Experimental Therapeutics and Reperfusion Injury,Brigham and Women ~ Hospital, 75Francis Street, Boston, MA 02115, USA.

Yoji Taba, Department of Clinical Pharmacology, Graduate School of MedicalSciences, Kyushu University, Fukuoka, Japan .

Yoshitaka Takahashi, Department of Molecular Pharmacology, KanazawaUniversity Graduate School ofMedical Science, Kanazawa 920-8640, Japan.

Elena Teslariu, Univ. Med. Phann. "Gr. T. Popa ", Universitatii 16, Iasi 6600,Romania.

Esther Titos, DNA Unit, Hospital Clinic, Institut d'Investigacions BiomediquesAugust Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona 08036, Spain.

CONTRIBUTORS xvii

Hirohumi Tsumagari, Department of Life Science and Biotechnology, ShimaneUniversity, Matsue, Shimane 690-8504, Japan.

Naonori Uozumi, Department ofBiochemistry and Molecular Biology, Faculty ofMedicine, The University ofTokyo, CREST ofJST, Tokyo 113-0033, Japan.*Present address

Linda Vargo, Digital Imaging CorelNBl0, Cleveland Clinic Foundation, 9500Euclid Avenue, Cleveland, OH 44195, USA.

Daya R. Varma, Department ofPharmacology and Therapeutics, McGill University,McIntyre Medical Sciences Building, 3655 Promenade Sir-William-Osler, Montreal,Quebec, H3G lY6, Canada.

Alejandro Vazquez-Tello, Research Center, Sainte-Justine Hospital, 3175 CoteSainte-Catherine, Montreal, Quebec, H3T 1C5, Canada.

A Maurizio Vignola, Istituto di Medicina Generale e Pneumologia, Universita diPalermo, Via Trabucco 180, 90146 Palermo, Italy.

Laurence Walch, CNRS FRE 2536 Hopital Broussais, 96 rue Didot, 75014 Paris,France.

Chi Chiu Wang, Department of Obstetrics & Gynaecology, Chinese University ofHong Kong, Hong Kong SAR.

Yoshiyasu Watanabe, Second Internal Medicine, Nihon University School ofMedicine, Ooyaguchi-kamimachi, 30-1, Itabashi-ku, Tokyo 173-8610, Japan.

Michael Wechsler, Department ofRespiratory and Critical Care Medicine, Brighamand Women's, Hospital, Harvard Medical School, 75 Francis Street, Boston, MA,02115, USA.

Oliver Werz, Institute ofPharmaceutical Chemistry, University ofFrankfurt, Marie­Curie-Str. 9, D-60439 Frankfurt, Germany.

Katarina Wikstrom, Division ofExperimental Pathology, Department ofLaboratoryMedicine, Lund University, Malmo University Hospital, entrance 78,fl. 3, 205 02Malmo, Sweden.

B. Mark Woerner, Pharmacia Research and Development, St Louis, Missouri, MO63167, USA.

Roswitha Wolfram, Department of Angiology, University of Vienna, WiihringerGiirtel 18~20, 1090 Vienna, Austria.

Dennis A. Wong, Department ofMedicine, University ofChicago 5841 S. MarylandAve. MC0930, Chicago, IL 60637, USA.

xviii CONTRIBUTORS

Wanpeng Xu, Department of Molecular Pharmacology. Kanazawa UniversityGraduate School ofMedical Science, Kanazawa 920-8640, Japan.

Saul Yedgar, Department ofBiochemistry. Hebrew University-Hadassah Medical,School, 91120 Jerusalem, Israel.

Hemant P. Yennawar, Department of Biochemistry and Molecular Biology, 108Althouse Building, The Pennsylvania State University, University Park, PA 16802.USA.

Chiaki Yokota, Cerebrovascular Laboratory, National Cardiovascular, CenterResearch Institute, 5-7-1 Fujishiro-dai Suita, Osaka 565-8565, Japan.

Kazushige Yokota, Department of Life Science and Biotechnology, ShimaneUniversity, Matsue, Shimane 690-8504, Japan.

Tanihiro Yoshimoto, Department of Molecular Pharmacology, KanazawaUniversity Graduate School ofMedical Science, Kanazawa 920-8640, Japan.

Axel Ziesenis, GSF-National Research Center for Environment and Healthlnstitutefor Inhalation Biology, Ingolstaedter Landstr. 1, D-85764 Neuherberg/Munich,Germany.

Preface

This volume contains selected lectures presented at the 12th InternationalConference on Advances in Prostaglandin, Leukotriene and Other BioactiveLipid Research: Basic Science and Clinical Applications which was held inIstanbul, Turkey, on August 25-29, 2002.

This meeting brought together basic and clinical scientists for the purposeof discussing advances in bioactive lipid research with. special attention tocancer, cardiovascular diseases, gastrointestinal diseases and respiratorydiseases. Topics covered included: the role of leukotrienes and lipoxins ininflammation, the cytochrome P450 pathway, the genetics and genomics ofbioactive lipids, lipid peroxidation, apoptosis, angiogenesis, isoprostanes,receptors and inhibitors, cyclooxygenase and lipoxygenase pathways andinhibitors, prostaglandin synthases and receptor signaling, phospholipasesand inhibitors. Sessions included plenary lectures with expertise in particularareas, oral presentation on selected topics and general poster sessions. J.M.Drazen (Boston, USA) discussed anti-leukotriene treatment in asthmapatients while C. Brink (paris, France) presented the recent advances inleukotriene receptors. The recent advances in cytochrome p450 pathwaydescribed in the session organized by J.C. McGiff (Valhalla, NY, USA). T.Shimizu (Tokyo, Japan) and M. Balazy (Valhalla, NY, USA) gave an updateon phospholipases and arachidonic acid peroxydation.

The editors are greatful to the Organizing, Programme and AdvisoryCommittees for their valuable contributions. We greatfully acknowledge thegenerous financial support provided by PharmaciaIPfizer, FakoPharmaceuticals Inc. and Novartis Pharmaceuticals Inc.

We are also greatful to all of the contributors to this volume, in particularto those who delivered their manuscripts by or before the requested deadline.

xix

xx PREFACE

We dedicate this volume to Professors Alan Bennett and SimonettaNicosia who passed away since the last gathering. It represents a snapshot ofthe field including a substantial amount of new data. We hope it will be auseful reference for investigators in both basic and clinical research.

Z. YazlCl, G. Folco, J.M Drazen,S. Nigam, and T. Shimizu

Contents

LEUKOTRIENES AND LIPOXINS: INFLAMMATION ANDASTHMA

1. Leukotrienes in AsthmaJ.M Drazen

2. Leukotriene Receptors: State of the Art 7C. Brink

3. LTC 4 Production by Eosinophils in Asthmatic Subjects withAlternative Forms ofAlox-5 Core Promoter 11

0. Kalayct, M Wechsler, B. Galper, C. Hong, E. Israel,J.M Drazen, and C.M Lilly

4. Il-4-Induced Lipid Mediators Class Switching in HumanNormal Mononuclear Phagocytes 15

A. Sala, M Profita, L. Siena , P.M Henson, R..C. Murphy,A. Paterno, A. Bonanno, L. Riccobono, A. Mirabella,G. Bonsignore, and A.M, Vignola

5. Lipoxins and Aspirin-Triggered Lipoxins in Airway Responses 19B.D. Levy, G.T. Desanctis, P.R. Devchand, E. Kim, K. Ackerman,B. Schmidt, W. Szczeklik, J.M Drazen, and CiN. Serhan

6. Potential Role of Cysteinyl Leukotrienes in Trafficking and

xxi

xxii

Survival ofHematopoietic Progenitor CellsA.M Boehmler, C. Denzlinger, L. Kanz, and R. Mahle

CONTENTS

25

7. Covalent Binding of Leukotriene~ to Nucleosides,Nucleotides, and Nucleic Acids 29

l.A. Hankin and R.C. Murphy

8. Firm Adhesion ofNeutrophils to Cerebral Vascular Endothelium"In Vivo": A Role for Cys-Leukotrienes 35

C. Carnini, G. Constantin, B. Rossi, M De Curtis , and G. Folco

CYTOCHROME P450 PATHWAY

9. The CYP P450 Arachidonate Monooxygenases :Enzymatic Relays for the control of Kidney Functionand Blood Pressure 39

J.H. Capdevila, K. Nakagawa, and V. Holla

10. Cytochrome P450-Derived Eicosanoids are Mediators ofOcular Surface Inflammation 47

ML. Schwartzman and M W. Dunn

11 . Regulation ofRenal Microvascular 20-HydroxyeicosatetraenoicAcid (20-Hete) Levels 55

MA. Carroll, M.K. Cheng, H. Jiang, A.B. Doumad,MF. Capparelli, and l .C. McGiff

12. Cyclooxygenase Activity is Regulated by the Heme OxygenaseSystem in Microvessel Endothelial Cells 59

N G. Abraham and R. Olszanecki

13. Cytochrome P450 Arachidonic Acid Metabolites ModulateRenal Tubular Function 67

MA. Carroll, NR. Ferreri, B.A. Escalante, Ao. Oyekan,and l .C. McGiff

RECEPTORS AND INHIBITORS

14. Thromboxane-induced ERK. Phosphorylation in HumanAortic Smooth Muscle Cells 71

C. Gallet, S. Blaie, S. Levy-Toledano, and A. Habib

CONTENTS xxiii

15. Arachidonic Acid Inhibits Cysteinyl-Leukotriene ReceptorActivation In Human Pulmonary Vessels 75

L. Walch, X Norel, J.-P. Gascard, and C. Brink

PHOSPHOLIPASES AND INHIBITORS

16. Cytosolic Phospholipase A2u in Mouse Platelets 81D.A. Wong, N Uozumi, Y. Kita , and T. Shimizu

17. Cellular Arachidonate-ReleasingFunctions of VariousPhospholipase A2s 87

M Murakami and1. Kudo

18. Biological Functions of Group X Secretory PLA2 93K. Hanasaki and H. Arita

19. Protection of Cell Membrane from Exogenous PLA2 andRelated Inflammatory Stimuli by Membrane-Anchored LipidConjugates 97

S. Yedgar, M Krimsky, and 0. Schwob

PROSTAGLANDIN SYNTHASES AND RECEPTOR SIGNALING

20. Regulatory Functions of Prostaglandin E2 Synthases 1031. Kudo and M Murakami

21. A Novel Type of Membrane-AssociatedProstaglandinE Synthase 107

K. Watanabe, Y. Ohmiya; H Ohkubo,N Tanikawa, M Kojima,and S. Ito

22. Expression, Purification and Characterization of RecombinantHuman Microsomal PGE2 Synthase-1 113

M Ouellet, A. Pen, P.-H. Ear, J.-P. Falgueyret, T.G. LeRiche,J.A. Mancini, D. Riendeau, and MD. Percival

CYCLOOXYGENASE AND LIPOXYGENASE PATHWAYS ANDINHIBITORS

23. Formation of Prostaglandin £2, Leukotriene B4and 8-Isoprostanein Alveolar Macrophages by Ultraflne Particles of ElementalCarbon 117

xxiv

I.Beck-Speier, N Dayal, E. Karg, KL Maier, H. Schulz,G. Schumann, A. Ziesenis, and J. Heyder

CONTENTS

24. Effects ofPGF2a Analogues in Experimental Morphine-InducedPhannacodependence 121

M Nechifor, D. Chelarescu, E. Teslariu, F. Cocu, and A. Negru

25. Inhibition ofProstaglandin H2 Synthases by Salicylate isDependent on the Oxidative State of the Enzymes 125

D.M Aronoff, 0. Boutaud, L.J. Marnett, and J.A. Oates

26. 5-Lipoxygenase Activation by MAPKAPK-2 and ERKs 1290. Wen, E. Burkert, L. Fischer, D. Szellas, D. Dishart,B. Samuelsson, 0. Radmark, and D. Steinhilber

27. Renal Effects of Selective Cyclooxygenase Inhibition inExperimental Liver Disease 133

M Lopez-Parra, J. Claria, A. Planaguma, E. Titos,J.L. Masferrer, B.M Woerner, A.T. Koki, W Jimenez,V. Arroyo, F. Rivera, and J. Rodes

28. Variable Antipyretic Effect ofSC-58236, a SelectiveCyclooxygenase (COX)-2 Inhibitor, in Rats 137

E.S. Akarsu, S. Mamuk, and S. Arat

GENETICS AND GENOMICS

29. Induction ofCyclooxygenase-2 Expression by Fluid ShearStress in Vascular Endothelial Cells 141

H. Inoue, Y. Taba, Y. Miwa, C. Yokota, M Miyagi,and T. Sasaguri

30. Induction of COX-2 Expression by the EndocannabinoidDerivative R(+)-Methanandamide 145

B. Hinz, R. Ramer, and K. Brune

31. Specific Gene Expression of Isofonns in CyclooxygenasePathway to Generate PGJ2 Derivatives During theDifferentiation of 3t3-Ll Adipocytes 153

S. Lu, M Ohya, K. Nishimura, M Jisaka, T. Nagaya,and K. Yokota

CONTENTS xxv

32. Tristetrapolin Binds to the COX-2 MRNA 3' UntranslatedRegion in Cancer Cells 157

0. Boutaud, D.A. Dixon, J.A. Oates, and H. Sawaoka

33. Platelet Activating Factor Receptors 161A.M Marrache, F. Gobeil Jr., S.G. Bernier, J. Stankova,M Rola-Pleszczynski, S. Choufani, G. Bkaily, A. Bourdeau,MG. Sirois, A. Vazquez-Tello, L. Fan, i-s. Joyal, J.G. Filep,D.R. Varma, A. Ribeiro-da-Silva, and S. Chemtob

34. Splicing Mutation of the Prostacyclin Synthase Gene in aFamily Associated with Hypertension 165

T. Nakayama, M Soma, Y. Watanabe, B. Hasimu,K. Kanmatsuse, S. Kokubun, J.D. Morrow, and J.A. Oates

35. DNA Methylation Regulates 5-Lipoxygenase PromoterActivity 169

J. Uhl, N. Klan, M. Rose, K.-D. Entian, 0. Werz, andD. Steinhilber

LIPID PEROXIDATION, APOPTOSIS AND FATTY ACIDS

36. Isomerization and Nitro-Oxidation of Arachidonic AcidbyNOz 173

M Balazy and J. Lopez-Fernandez

37. Prostaglandin Fza Protected Cultured Madin-Darby CanineKidney Cells from the Development of Apoptosis Inducedby 12-0-Tetradecanoyl Phorbol-Boscetate and StimulatedSynergistically with Nordihydroguaiaretic Acid 177

K. Nishimura, H. Tsumagari, A. Monoka. S. Lu, M Jisaka,T. Nagaya, and K. Yokota

38. LDL Receptor-Related Protein Plays an Essential Role in 12/15-Lipoxygenase-Mediated LDL Oxidation by Macrophages 181W. Xu, Y. Takahashi, T. Iwasaki, H. Hattori, and T. Yoshimoto

39. Effects of in vitro Exposure to Carbon Dioxide on theExpression of Apoptosis-Associated Genes in HumanPeritoneal Fibroblasts 185

A.MB. Souza, c.u. Briton-Jones, e.e. Wang, c.r.Haines,and MS. Rogers

xxvi CONTENTS

40. Identification, Characterization, and Properties of a ClassAlpha Microsomal Glutathione S-Transferase 189

KS. Prabhu, P. V. Reddy, A.D. Liken, E.C. Jones,H.P. Yennawar, and C. C. Reddy

CARDIOVASCULAR SYSTEM

41. Cyclooxygenase (COX) Function in The Ductus Arteriosus :Another Look 193

F. Coceani, B. Baragatti, F. Brizzi, S. Barogi, and C. Ackerley

42. Evidence for Enhanced Oxidative Stress in Coronary HeartDisease and Chronic Heart Failure 197

R. Wolfram, A. Oguogho, B. Palumbo, and H. Sinzinger

ANGIOGENESIS AND CANCER

43. The Leukotriene Receptor CYSLT, and 5-Lipoxygenase areUpregulated in Colon Cancer 201C.K NIelsen, J.F. Ohd, K WIkstrom, R Massoumt,S. Paruchurt, M Juhas, andA. Sjolander

44. Increased Expression of 5-Lipoxygenase in GlioblastomaMultifonne 205

M Golubic, R.A. Prayson, L. Vargo, J. Bondar, andG.H. Barnett

ISOPROSTANES

45. Variable Influence of Statins on Isoprostanes in Hyperlipidemia 209H. Sinzinger and A. Oguogho

46. Increased Isoprostanes in Children of Smoking ParentsH. Sinzinger, A. Oguogho, andH. Pilz

47. The Dinor Isoprostane Pathway in PlantsC. LoefJ/er, 1. Thoma, M Krischke, and MJ. Mueller

Index

213

217

221