Recent research has given great insight into the physiological and pharmaceutical effects of histamine on the central nervous system and especially on the brain. This volume focuses on these many new findings, including the role of brain histamine in the arousal system, learning, and memory. Also featured are the mechanisms of histamine release in bone marrow and mast cells and the role of histamine in neutrophil differentiation. These are analyzed using the most up-to-date techniques of molecular pharmacology and refined immunoelectroscopy. In addition, the pharmacological profiles of newly developed H1 antagonists are described, making this book invaluable to those who want to understand the very latest advances in histamine research.
Since its identification by Sir Henry H. Dale a century ago, histamine has become one of the most important multifunctional biogenic amines in the field of biomedicine. The pharmacological effects of histamine are mediated through four types of membrane histamine receptors; H1R, H2R, H3R and H4R, which are all heptahelical G-protein-coupled receptors. It has been known to play the broadest spectrum of activities in various physiological and pathological conditions including cell proliferation, differentiation, hematopoiesis, embryonic development, regeneration, wound healing, aminergic neurotransmission and numerous brain functions, secretion of pituitary hormones, regulation of gastrointestinal and circulatory functions, cardiovascular system, as well as inflammatory reactions, modulation of the immune response, endocrine function and homeostasis, and other important areas. This book is a compendium of the current state of established and investigational literature on Histamine, its receptors and their Agonists and antagonists. It provides a comprehensive overview of histamine biology in the field of biochemistry, cell biology, molecular biology, immunology, allergy, neurobiology, pharmacology, microbiology and reproductive biology. The first section on Histamine biology and physiology leads into subsequent sections on enzymology, pharmacology, regulation of the immune system and cell proliferation and role in allergic and other diseases including acid peptic diseases, inflammatory diseases, autoimmune and cancer diseases, nervous system, reproductive functions and hematopoiesis. The compilation of chapters in the book presents the most recent advances in histamine research and bridges the basic and clinical aspects of histamine biology.
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.
Research in the field of histamine receptors over the past 100 years went hand-in-hand with the development of modern pharmacology. Advances in histamine research led by outstanding scientists was so incisive that the clinical approach to treat allergies and gastrointestinal ailments was revolutionized. The pharmacological treatment of peptic ulcer and gastroesophageal reflux was indeed a revolution, as it ended the surgical intervention. Interest in histamine pharmacology was resurrected by the discovery of another histamine receptor, number 4, using genomics-based reverse pharmacological approaches for screening orphan GPCRs. This receptor is preferentially expressed by immune cells and its discovery raised hopes for its translational exploitation as a new therapeutic target for unmet medical needs ranging from asthma to cancer. However, several drawbacks emerged and dramatically slowed down research in the field. A better understanding of receptor intra-and interspecies heterogeneity will certainly improve and accelerate the translation of experimental data into clinical practice. Also, the plethora of data on brain histamine is hinting at a fundamental role of this system as a hub that receives internal and peripheral stimuli to allocate the necessary excitation to specific brain circuits that preside the appropriate behavioral responses. The development of new histaminergic ligands is an ongoing process that constantly provide new preclinical tools. The aim of this book is to cover the most important aspects of histamine receptor function and pharmacology in the central nervous system and to provide a comprehensive overview of the preclinical and clinical advances made in recent decades and the exciting prospects for the future. It highlights the clinical areas where there is a great need for new therapeutic approaches and where novel histaminergic agents may be useful for personalized medicine.
Histamine is an intriguing compound; the same is true for the several classes of anti-histaminergic compounds. The classical anti-histamines, now known as H -antagonists have 1 been the result of intensive research in the 1950s and 1960s. The new, so-called non-sedating H1-antagonists, which became available in the 1980s, could be d'eveloped mainly due to insights into structural features causing the sedating effects of the older compounds. In the 1970s the H2-receptors became important targets for developing new anti-ulcer agents. The H2-antagonist story is a stimulating example of modern research on pharmacology and medicinal chemistry. Unknown and new properties of histamine and histaminergic systems came to the attention of the pharmacologists and medicinal chemists in the 1980s. The role of histamine as a neurotransmitter, the existence of a presynaptic receptor (H ) controlling the release of histamine 3 and other neurotransmitters, and the particular character of this receptor became important as the possibilities to design new therapeutic agents were realized. Recently, other roles of the histaminergic systems have been suggested. Is there a distinct histamine receptor involved in immunological features of histamine? Is histamine involved in the prolactin axis? Are histamine receptors intracellularly present in certain cells and what is their possible role? For these reasons it was the right time to discuss "New Perspectives in Histamine Research" during a scientific meeting. Therefore a symposium was organized as a satellite of the XIth International Congress of Pharmacology of IUPHAR in Amsterdam in 1990.
Histamine Receptors—Advances in Research and Application: 2012 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about Histamine Receptors in a compact format. The editors have built Histamine Receptors—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Histamine Receptors in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Histamine Receptors—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Hardbound. This book reviews the knowledge of the various fields of histamine research and discusses the basic mechanisms involved in histamine action. It covers histamine release, the central nervous system, gastric secretion and histamine receptors, heart and ultramicrodetermination.
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.
Hardbound. Focuses on recent studies into the actions and roles of histamine in the gastrointestinal, cardiovascular, central nervous and immune systems. Recent advances herald another major breakthrough in histamine research and include new histochemical approaches to visualisation of histamine-synthesising and storing cells, more specific enzyme inhibitors and new methods for studying histamine biosynthesis and metabolism. Drugs to block the effect of histamine have a well established place in such clinical areas as allergy, inflammation, and gastroenterology. Current research anticipates new exciting opportunities for therapy in neurobiology and immunology.
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.
