This book provides the reader with background information on neurotransmitter release. Emphasis is placed on the rationale by which proteins are assigned specific functions rather than just providing facts about function.
Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.
As opposed to other books on the topic, this volume is unique in also covering emerging transporter targets. Following a general introduction to the importance of targeting transporter proteins with drugs, the book systematically presents individual transporter classes and explains their pharmacology and physiology. The text covers all transporter families with known or suspected importance as drug targets, including neurotransmitter transporters, ABC transporters, glucose transporters and organic ion transporters. The final part discusses recent advances in structural studies of transport proteins, assay methods for transport activity, and the systems biology of transporters and their regulation. With its focus on drug development issues, this authoritative overview is required reading for researchers in industry and academia targeting transport proteins for the treatment of disease.
General Description of the Series: Neurotransmitter Transporters focuses on biochemical, electrophysiological, pharmacological, molecular, and cell biological approaches used to study neurotransmitter transport systems. The articles provide detailed descriptions of procedures that should enable the reader to understand how they are accomplished and to repeat or adapt them for their own experimental needs. This book is the first to focus on methods that have been the basis for the rapid development of this area. General Description of the Series: The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today--truly an essential publication for researchers in all fields of life sciences. Key Features * The transport of CNS neurotransmitter transporters * Electrophysiological, biochemical, molecular, cellular biological, pharmacological, neurochemical, and structural approaches * Both plasma and vesicular carriers
The present volume of the Handbook of Experimental Pharmacology gives a representative survey of the current status of the structure, function, regulation and molecular pharmacology of Neurotransmitter Transporters and aims at providing an overview of insights that were generated in the past 5 years. If the volume serves as both, a useful compendium of current concepts and an inspiring starting point, it will have fulfilled its mission and will be a source for students interested in this emerging field as well as for experienced scientists looking for an update. This volume is the brainchild of the editor-in-chief of the HEP series, Klaus Starke, awe-inspiring to all pharmacologists of younger generations.
Neurotransmission is a multicomponent process. Transmitters, released by neuronal activity, act on pre- and postsynaptic receptors, and many books detail advances in the receptor field. In addition, after their release from nerve endings, transmitters are removed from the neuronal vicinity by uptake into neuronal or glial cells by specific tra- porter proteins that have been studied intensely over the last 30 years; this information is scattered throughout numerous publishing vehicles. Therefore, the primary aim of this second edition of N- rotransmitter Transporters: Structure, Function, and Regulation is to offer a comprehensive picture of the characterization of neurotransmitter transporters and their biological roles. The transporter field has moved forward in stages. In the first phase, progress came from the use of substrate or blocker ligands selectively targeting transporters, the application of model systems allowing the study of transmitter tra- port shielded from storage, and the development of mathematical models for describing transport phenomena. In the second phase, roughly covering the last decade, advances in DNA techniques allowed the cloning of numerous genes coding for different transporter proteins. In the current, third stage, a wealth of information is being accumulated in studies relating transporter structure with function, experiments addressing regulation by posttranslational transfor- tion, investigations into transport modulation by trafficking processes and genomic influences, characterization of channel properties of tra- porters by electrophysiological approaches, and the creation of transgenic animals under- or overexpressing a given transporter protein.
It has been known for half a century that neurotransmitters are released in preformed quanta, that the quanta represent transmitter-storing vesicles, and that release occurs by exocytosis. The focus of this book is twofold. In the first part, the molecular events of exocytosis are analysed. In the second part of the book, the presynaptic receptors for endogenous chemical signals are presented that make neurotransmitter release a highly regulated process.
Development of the Nervous System, Second Edition has been thoroughly revised and updated since the publication of the First Edition. It presents a broad outline of neural development principles as exemplified by key experiments and observations from past and recent times. The text is organized along a development pathway from the induction of the neural primordium to the emergence of behavior. It covers all the major topics including the patterning and growth of the nervous system, neuronal determination, axonal navigation and targeting, synapse formation and plasticity, and neuronal survival and death. This new text reflects the complete modernization of the field achieved through the use of model organisms and the intensive application of molecular and genetic approaches. The original, artist-rendered drawings from the First Edition have all been redone and colorized to so that the entire text is in full color. This new edition is an excellent textbook for undergraduate and graduate level students in courses such as Neuroscience, Medicine, Psychology, Biochemistry, Pharmacology, and Developmental Biology. - Updates information including all the new developments made in the field since the first edition - Now in full color throughout, with the original, artist-rendered drawings from the first edition completely redone, revised, colorized, and updated
Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction.
This book is designed as an introductory text in neuroendocrinology; the study of the interaction between the brain and endocrine system and the influence of this on behaviour. The endocrine glands, pituitary gland and hypothalamus and their interactions and hormones are discussed. The action of steroid and thyroid hormone receptors and the regulation of target cell response to hormones is examined. The function of neuropeptides is discussed with respect to the neuroendocrine system and behaviour. The neuroimmune system and lymphokines are described and the interaction between the neuroendocrine and neuroimmune systems discussed. Finally, methods for studying hormonal influences on behaviour are outlined. Each chapter has review and essay questions designed for advanced students and honours or graduate students with a background in neuroscience, respectively.