Glutamate and GABA get together

Glutamate and GABA Receptors and Transporters: Structure, Function and Pharmacologyedited by Jan Egeberg, Arne Shousboe and Povl Krogsgaard-Larsen, Taylor & Francis, 2002. £99 (hardback) (xii + 427 pages) ISBN 074840819The processes that regulate the major excitatory and inhibitory neurotransmitter systems in the brain are the subject of this new book. The amino acids glutamate and GABA are inextricably linked in the control of neuronal excitability and this volume provides an up-to-date review of the basic physiology and pharmacology of these two important neurotransmitters. The editors have assembled an impressive list of contributing authors who have provided 18 chapters covering everything from the structure and function of glutamate and GABA receptors to the use of transgenic models to study the role of these transmitter systems in disease.The book begins with an excellent chapter reviewing the function and pharmacology of ionotropic glutamate receptors. Additional chapters in this first section are devoted to detailed reviews of the structure of these receptors and of processes that regulate their cellular trafficking. Particularly useful are tables summarizing the results of the extensive mutagenesis experiments that have helped identify the modular components of these receptors. The results of these mutagenesis studies were elegantly complemented and verified by the recent determination of the crystal structure of a kainate-bound GluR2 subunit in which the extracellular domains had been linked via short spacers. The extensive pharmacology of NMDA and non-NMDA receptors are covered in separate chapters and provide a chemist's eye-view of how receptor-selective compounds are developed. These sections are followed by two chapters devoted to the metabotropic glutamate receptors that have received a great deal of attention recently as important modulators of synaptic plasticity.The section covering the physiology and pharmacology of ionotropic GABA receptors begins with a review of studies performed with cerebellar granule cells as a model of how GABAA receptors provide inhibitory control within the golgi-cell–granule-cell loop of the cerebellum. This chapter, although well written, seems somewhat out of place as an introduction to GABAA receptors because it is followed by a section than takes a more global approach of reviewing what is known of GABAA receptor structure and function. As with the glutamate receptors, this section also contains individual chapters devoted to metabotropic GABAB receptors. Although the existence of GABAB receptors was first proposed in the 1980s, based on the ability of l-baclofen to activate a bicuculline-insensitive response, the cDNAs for members of this family were not isolated until 1997. As noted in these chapters, the subsequent use of molecular tools has facilitated our understanding of these enigmatic receptors.Rounding out the discussion are two chapters focused on the transporters that regulate the extracellular availability of glutamate and GABA. The inclusion of these chapters in this single volume is particularly appreciated because the function of these important proteins is often over-shadowed by their more well known ionotropic relatives. In fact, amino acid transporters are surprisingly complex and display a range of electrophysiological behaviors in addition to their transmitter transport activities. As with other neurotransmitters, pharmacological agents that modulate transporter activity are under active development.The final chapters of the book focus on taking what is known of the structure and function of glutamate and GABA receptors and transporters and applying it to studies of behavior and pathophysiology. Particularly interesting are two chapters devoted to the use of experimental animals that lack all or part of specific receptor subunits. These animals are often the only way that the role of specific subunits in various behaviors can be addressed because subunit-selective antagonists are not available for all receptor combinations. The final chapters of this volume offer insights into the role of the glutamate and GABA systems in disease and how receptor-selective compounds might be useful in their treatment. Much of this is speculative at present but there is growing evidence that both hyper- and hypo-functioning of either the glutamate or GABA receptor systems can lead to neuronal pathology and might contribute to such diverse illnesses as schizophrenia and Alzheimer's disease.A few minor issues need to be addressed by the editors in future versions of this book. In particular, there is a considerable amount of redundancy with respect to the presentation of the basic molecular and structural organization of the glutamate and GABA receptors. In this respect, the book resembles that of a proceedings rather than a smoothly edited textbook. Changes are also needed in the organization and integration of the figures because all of the color figures are contained in one continuous section rather than being included in their respective chapters.These shortcomings notwithstanding, this text does serve a useful role as a central repository of relatively advanced information pertaining to the major excitatory and inhibitory neurotransmitter systems of the brain. It is likely that it would do well as the source book for a graduate-level course on excitatory and inhibitory transmitter systems, and students and teachers of neuroscience and neuropharmacology would find it a welcome addition to their library.