Histamine H4 Receptor

H4 R is the newest member of the histamine receptor family, which was discovered about twelve years ago. It is considered a very promising drug target. The effort to improve the pharmacokinetic properties of the currently available H4 R ligands is reflected in a steadily growing number of scientific publications and patent applications. Preclinical data strongly confirms the need for novel potent H4 R ligands to explore their therapeutic value in allergy, inflammation, autoimmune disorders, and possibly, cancer. Readers will be provided with extensive knowledge on histamine metabolism, as well as cellular histamine transport, storage and release, effects of histamine and histamine receptor ligands, with particular attention to the H4 R, on inflammatory cells including mast cells, basophils, eosinophils, neutrophils, macrophages, dendritic cells, and T cells. The present knowledge on the regulatory role of histamine and the therapeutic exploitation of histamine receptor ligands in atopic diseases, with emphasis on human and animal models of asthma, allergic dermatitis and pruritus are discussed.

This ​book provides a comprehensive overview on current histamine and histamine receptor research in context of human health and disease and reflect the multidisciplinary nature of the field. While the editors realize that it is almost impossible to cover the field completely within the constraints of a single HEP volume, nonetheless, all important aspects will be covered in one way or the other. An overarching introductory chapter will link the individual chapters and provide an overview on the field. This chapter will also link the book to the previous HEP volume on histamine receptors and the recent HEP volume on the pharmacology of itch. Great attention will be paid to complementation of existing literature while avoiding undue duplication. The book will cover new methods for analysis of histamine and histamine metabolites, development of methods for histamine receptor analysis, signal transduction, histamine release, regulation of immune cells by histamine, histamine metabolism and associated diseases, regulation of major organ systems by histamine and development of new drugs and experimental tools for the study of histamine receptors.

This book illustrates the current state-of-the-art in histamine research, with a focus on the appropriate methodologies to investigate the pharmacological properties and the therapeutic exploitation of HRs and their ligands. In addition, the range of techniques described provides an introduction to complementary cross-methodological disciplines beyond these fields. This multi-disciplinary approach is required to define the ‘decision gates’ that determine the development of more effective and safer therapeutic options for many forms of highly prevalent and debilitating diseases, such as asthma, dementias, dermatitis, and arthritis. Written for the Methods in Pharmacology and Toxicology series, chapters concentrate on practical, hands-on protocols from experts in the techniques. Authoritative and thorough, Histamine Receptors as Drug Targets seeks to aid pharmacologists, biochemists, drug discovery researchers, molecular biologists, chemists, toxicologists, lab scientists, medical doctors, principle investigators, research scientists, lab directors and technicians, as well as graduate students around the world in pursuing the study of this vital scientific area.

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.

A comprehensive and detailed overview of the current state of preclinical research on histamine and histamine receptors. Part of the book focuses on novel approaches to the study of histamine receptors such as polymorphism, genetic linkage, and computational analysis, and on the use of new histaminergic ligands in diseases such as asthma and dermatitis. Several chapters will be devoted to the role of histamine in the control of homeostatic and behavioral responses such as the sleep-wake cycle, regulation of the blood brain barrier, food intake, alertness, itch, and memory formation and consolidation.

Brain aminergic pathways are organized in parallel and interacting systems, which support a range of functions, from homoeostatic regulations to cognitive, and motivational processes. Despite overlapping functional influences, dopamine, serotonin, noradrenaline and histamine systems provide different contributions to these processes. The histaminergic system, long ignored as a major regulator of the sleep-wake cycle, has now been fully acknowledged also as a major coordinator of attention, learning and memory, decision making. Although histaminergic neurons project widely to the whole brain, they are functionally heterogeneous, a feature which may provide the substrate for differential regulation, in a region-specific manner, of other neurotransmitter systems. Neurochemical preclinical studies have clearly shown that histamine interacts and modulates the release of neurotransmitters that are recognized as major modulators of cognitive processing and motivated behaviours. As a consequence, the histamine system has been proposed as a therapeutic target to treat sleep-wake disorders and cognitive dysfunctions that accompany neurodegenerative and neuroinflammatory pathologies. Last decades have witnessed an unexpected explosion of interest in brain histamine system, as new receptors have been discovered and selective ligands synthesised. Nevertheless, the complete picture of the histamine systems fine-tuning and its orchestration with other pathways remains rather elusive. This Research Topic is intended to offer an inter-disciplinary forum that will improve our current understanding of the role of brain histamine and provide the fundamentals necessary to drive innovation in clinical practice and to improve the management and treatment of neurological disorders.

Together with the two previous volumes of the Handbook of Experimental Pharmacology on histamine and antihistamines the present publication yields a picture of a still rapidly developing field of research. New techniques and new experimental approaches have brought us new knowledge and deeper insight into the biomedical significance of histamine, even if many questions remain to be answered about the functional and medical implications of this old biogenic amine. The present volume covers the progress in histamine research during the past two decades. A significant chapter concerns techniques for histamine determination. As the result of a consensus meeting in Munich in December 1988, a panel of eminent specialists arrived at common recommendations as to the usefulness of the available histamine assays for the most common experimental biomedical conditions. The heterogeneity of mast cells, with great differences in their reactivity to various stimuli, has become apparent, not only among species but also among the tissues of a species. New informa tion is presented about the mechanism of exocytosis. The old questions about the role of histamine in the mechanism of gastric secretion and in cardio vascular and respiratory functions have been studied with new techniques, and the role of HI and H2 receptors discussed. New observations have been made on the occurrence and possible functions of histaminergic neurons and histamine receptors in CNS where a new type of receptor, the H , seems to 3 be widely represented.

Brain Protection Strategies and Nanomedicine, Volume 266 in the Progress in Brain Research serial highlights new advances in the field, with this new volume presenting interesting chapters on a variety of topics, including Histamine H3 and H4 receptors modulate Parkinson’s disease induced brain pathology: Neuroprotective effects of nanowired BF-2649 and clobenpropit with anti-histamine-antibody therapy, Ultra Early Molecular Biologic Diagnosis Of Malignant And Neurodegenerative Diseases By The Immunospecific Profiles Of The Proteins Markers Of The Surface Of The Mobilized Autologous Hematopoietic Stem Cells, Neuroprotective effects of Insulin like growth factor-1 on Engineered metal Nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, and more. Other chapters cover how Methamphetamine exacerbates pathophysiology of traumatic brain injury at high altitude: Neuroprotective effects of nanodelivery of a potent antioxidant compound H-290/51, Effectiveness of bortezomib and temozolomide for eradication of recurrent human glioblastoma cells, resistant to radiation, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in Progress in Brain Research serials Includes the latest information on brain protection strategies and nanomedicine