Histamine in Inflammation (Advances in Experimental Medicine and Biology, 709)

The year 2010 marks the centennial for the identification of histamine and the first glimpse of its many physiological functions. From these initial findings a rich tapestry of research has uncovered roles for histamine in almost every physiological process with new findings emerging every year. These diverse roles of histamine have made for fertile ground for the discovery of novel therapeutics, and these drugs have been so successful that the term “antihistamine” has entered the common lexicon. This volume is an attempt to give a snapshot in time as to the current understanding of the role of histamine in just one important therapeutic area—inflammation. The first three chapters provide some background context for the rest of the book starting out with a historical perspective by Figueroa and Shankley. Bongers et al provide an overview of the pharmacology of the four histamine receptors and the chapter by Hiroshi Ohtsu describes how histamine is synthesized as well as the insights derived from mice where this synthesis is disrupted. The next several chapters discuss disease areas where histamine is known to be involved. Chapter 4 by Thomas Taylor-Clark outlines the role of histamine in allergic rhinitis, an area were antihistamines are commonly used. This is also true for ocular allergy as discussed by Ohbayashi et al. Both of these chapters highlight aspects of these conditions that are still not well-controlled and suggest the utility of new antihistamines targeting other histamine receptors. Title Page 3 Copyright Page 4 DEDICATION 5 PREFACE 6 ABOUT THE EDITOR... 8 PARTICIPANTS 9 CONTENTS 12 Chapter 1 One Hundred Years of Histamine Research 16 Abstract 16 Introduction 16 Exploring the Physiological Effects of Histamine 17 The First Antihistamines 17 Pharmacological Definition of Histamine H1 and H2 Receptors 17 Pharmacological Definition of the Histamine H3 Receptor 18 Pharmacological Definition of the Histamine H4 Receptor 19 The Molecular Biological Characterization of Histamine Receptors 19 Alternative Intracellular Signaling of Histamine Receptors 20 Generations of Histamine Targeted Genetically Modified Mice 20 Conclusion 21 Acknowledgement 22 References 23 Chapter 2 Molecular Pharmacology of the Four Histamine Receptors 25 Abstract 25 The Discovery of the Four Histamine Receptors: An Historical Overview 25 Histamine Receptors, Signal Transduction and Their Ligands 26 The Histamine H1 Receptor and Its Ligands 26 The Histamine H2 Receptor and Its Ligands 27 The Histamine H3 Receptor and Its Ligands 28 The Histamine H4 Receptor and Its Ligands 30 Conclusion 30 References 30 Chapter 3 Histamine Synthesis and Lessons Learned from Histidine Decarboxylase Deficient Mice 34 Abstract 34 Introduction 34 HDC Transcriptional Regulation 35 Epigenetic Regulation of HDC Gene Expression 35 l-Histidine Decarboxylase Gene Knockout Mice 36 Histamine and Immunity 36 Histamine in Wound Healing 36 Histamine in Malaria 37 Histamine in Crohn’s Disease 38 Histamine in Allergic Bronchial Asthma 38 Histamine in Systemic Anaphylaxis Model 40 Histamine in Atherosclerosis 40 Histamine Uptake into and Release from Histamine Producing Cells 41 Conclusion 41 References 42 Chapter 4 Histamine in Allergic Rhinitis 45 Abstract 45 Introduction 45 Histamine and the Early Phase Response in Allergic Rhinitis 46 H1 Receptors: Sensory Nerve Activation and Central Reflexes 46 H1 Receptors and the Nasal Vasculature 48 Other Histamine Receptors in the Early Phase Response 48 Histamine Receptors and Immune Modulation 49 Conclusion 50 References 50 Chapter 5 The Role of Histamine in Ocular Allergy 54 Abstract 54 Introduction 54 Clinical Manifestations of Ocular Allergy 54 Seasonal and Perennial Allergic Conjunctivitis 55 Vernal Keratoconjunctivitis 55 Atopic Keratoconjunctivitis 55 Current Treatments for Ocular Allergy 56 Allergic Responses in the Conjunctiva 56 Mast Cells in the Conjunctiva 58 Histamine in the Conjunctiva 58 Histamine and the Conjunctival Barrier 58 Histamine Receptors in the Conjunctiva 59 Histamine H1 and H2 Receptors 59 Histamine H4 Receptor 60 Tissue-Specific Roles of Histamine Receptors 60 Conclusion 62 References 62 Chapter 6 The Role of Histamine in Asthma 64 Abstract 64 Introduction 64 Histamine in the Asthmatic Airway 64 Physiologic Role for Histamine in Lung and Asthma 65 Immunological Modulation by Histamine 66 Mast Cells and Basophils 66 Eosinophils 67 Neutrophils 68 Monocytes and Macrophages 68 Dendritic Cells 68 T Cells 69 iNKT Cells 70 Histamine in Animal Models of Asthma 70 Antihistamines and Clinical Asthma 71 Conclusion 73 References 73 Chapter 7 Antihistamines in the Treatment of Urticaria 78 Abstract 78 Introduction 78 Acute Urticaria 80 Chronic Spontaneous Urticaria 80 Management of Urticaria Follows Basic Principles 81 Antihistamines Play the Major Role in Urticaria Treatment 81 Further Therapeutic Possibilities Are Limited 82 Modern Antihistamines Should also Be Used for Children 82 Conclusion 82 References 82 Chapter 8 Histamine and Antihistamines in Atopic Dermatitis 84 Abstract 84 Histamine 84 Histamine Receptors 85 Histamine in Atopic Dermatitis 86 Antihistamines and Histamine Receptor Antagonism in Atopic Dermatitis 87 Clinical Studies of Antihistamines in Atopic Dermatitis 88 Conclusion 88 References 89 Chapter 9 Histamine, Immune Cells and Autoimmunity 92 Abstract 92 Introduction 92 Histamine and Immune Cells 93 Histamine and Dendritic Cells 93 Histamine and T Cells 94 Histamine and Immunoregulatory T Cells 94 Histamine and B Cells 95 Histamine and Monocytes/Macrophages 95 Histamine and Basophils/Mast Cells 96 Histamine and Eosinophils/Neutrophils 97 Histamine and Autoimmunity 97 Histamine and Experimental Autoimmune Encephalomyelitis (EAE) 98 Histamine and Autoimmune Chronic Urticaria (CU) 99 Histamine and Rheumatoid Arthritis (RA) 100 Histamine and Experimental Autoimmune Myocarditis 100 Conclusion 100 References 101 Chapter 10 Histamine in Neurotransmission and Brain Diseases 106 Abstract 106 Histaminergic Neurons 106 Histamine Synthesis, Storage, Release and Catabolism 107 Histamine Receptors in the Brain 108 Physiological Role of Neuronal Histamine 109 Arousal 109 Control of Pituitary Hormone Secretion 109 Appetite and Body Weight 109 Histamine in Brain Diseases 110 Sleep-Wake Disorders 110 Alzheimer’s Disease 110 Schizophrenia 111 Parkinson’s Disease 112 Epilepsy 113 Brain Injury 113 Pain 113 Conclusion 113 Acknowledgements 114 References 114 Chapter 11 Histamine in Normal and Malignant Cell Proliferation 119 Abstract 119 Histamine and Cell Proliferation 119 Histamine in Normal Cell Proliferation 119 Gastric Mucosa 120 Hematopoietic Proliferation 121 Fibroblasts and Fibrosis 122 Mammary Gland and Uterus 122 Skin 123 Tumor Formation—Principles 123 Histamine in Benign and Malignant Tumors 124 Proliferation of Malignant Cell Lines 124 In-Vivo Experimental Models 125 Human Tumors 127 Breast and Colorectal Cancer 127 Melanoma 128 Lung Cancer 128 Lymphomas and Leukemia 129 Histamine Blood Levels in Cancer Patients 129 Angiogenesis 129 Effect of Histamine on Immune Regulation 130 Conclusion 130 References 130 Chapter 12 The Future Antihistamines: Histamine H3 and H4 Receptor Ligands 134 Abstract 134 Introduction 134 Potential Indications for H3R Ligands 135 Sleep/Wake Disorders 135 Cognitive Impairment 137 Alzheimer’s Disease (AD) and Schizophrenia 137 Attention-Deficit Hyperactivity Disorder (ADHD) 137 Other Indications 138 Epilepsy 138 Obesity 138 Neuropathic Pain 138 Allergic Rhinitis 139 Cancer 139 Potential Indications for H4R Ligands 139 Asthma 139 Atopic Dermatitis 142 Allergic Rhinitis 143 Autoimmune Diseases 143 Pain 144 Cancer 144 Conclusion 144 References 145 Index 150 One Hundred Years Of Histamine Research / Katherine Figueroa And Nigel Shankley -- Molecular Pharmacology Of The Four Histamine Receptors / Gerold Bongers, Iwan De Esch, And Rob Leurs -- Histamine Synthesis And Lessons Learned From Histidine Decarboxylase Deficient Mice / Hiroshi Ohtsu -- Histamine In Allergic Rhinitis / Thomas Taylor-clark -- The Role Of Histamine In Ocular Allergy / Masaharu Ohbayashi ... [et Al.] -- The Role Of Histamine In Asthma / Paul J. Dunford And Stephen T. Holgate -- Antihistamines In The Treatment Of Urticaria / Torsten Zuberbier And Marcus Maurer -- Histamine And Antihistamines In Atopic Dermatitis / Jørg Buddenkotte, Marcus Maurer, And Martin Steinhoff -- Histamine, Immune Cells, And Autoimmunity / Elke Schneider, Maria Leite-de-moraes, And Michel Dy -- Histamine In Neurotransmission And Brain Diseases / Saara Nuutinen And Pertti Panula -- Histamine In Normal And Malignant Cell Proliferation / Andras Falus, Zoltøn Pøs, And Zsuzsanna Darvas -- The Future Antihistamines : Histamine H3 And H4 Receptor Ligands / Fuqu Yu, Pascal Bonaventure, And Robin L. Thurmond. Edited By Robin L. Thurmond. Includes Bibliographical References And Index. One hundred years of histamine research / Katherine Figueroa and Nigel Shankley Molecular pharmacology of the four histamine receptors / Gerold Bongers, Iwan de Esch, and Rob Leurs Histamine synthesis and lessons learned from histidine decarboxylase deficient mice / Hiroshi Ohtsu Abstract Histamine in allergic rhinitis / Thomas Taylor-Clark The role of histamine in ocular allergy / Masaharu Ohbayashi ... [et al.] The role of histamine in asthma / Paul J. Dunford and Stephen T. Holgate Antihistamines in the treatment of urticaria / Torsten Zuberbier and Marcus Maurer Histamine and antihistamines in atopic dermatitis / Jørg Buddenkotte, Marcus Maurer, and Martin Steinhoff Histamine, immune cells, and autoimmunity / Elke Schneider, Maria Leite-de-Moraes, and Michel Dy Histamine in neurotransmission and brain diseases / Saara Nuutinen and Pertti Panula Histamine in normal and malignant cell proliferation / Andras Falus, Zoltøn Pøs, and Zsuzsanna Darvas The future antihistamines : histamine H3 and H4 receptor ligands / Fuqu Yu, Pascal Bonaventure, and Robin L. Thurmond. Front Matter....Pages i-xviii One Hundred Years of Histamine Research....Pages 1-9 Molecular Pharmacology of the Four Histamine Receptors....Pages 11-19 Histamine Synthesis and Lessons Learned from Histidine Decarboxylase Deficient Mice....Pages 21-31 Histamine in Allergic Rhinitis....Pages 33-41 The Role of Histamine in Ocular Allergy....Pages 43-52 The Role of Histamine in Asthma....Pages 53-66 Antihistamines in the Treatment of Urticaria....Pages 67-72 Histamine and Antihistamines in Atopic Dermatitis....Pages 73-80 Histamine, Immune Cells and Autoimmunity....Pages 81-94 Histamine in Neurotransmission and Brain Diseases....Pages 95-107 Histamine in Normal and Malignant Cell Proliferation....Pages 109-123 The Future Antihistamines: Histamine H 3 and H 4 Receptor Ligands....Pages 125-140 Back Matter....Pages 141-143 The year 2010 marks the centennial for the identification of histamine and the first glimpse of its many physiological functions. From these initial findings a rich tapestry of research has uncovered roles for histamine in almost every physiological process with new findings emerging every year. These diverse roles of histamine have made for fertile ground for the discovery of novel therapeutics, and these drugs have been so successful that the term "antihistamine" has entered the common lexicon. This book is an attempt to give a snapshot in time as to the current understanding of th