The elucidation of the cellular and molecular bases underlying the inte grated function of the central nervous system, both in disease and in health, must ultimately come from the combined efforts of scientists from many disciplines, including biology, chemistry, histology, pathology, physiology, pharmacology, and psychology. Communication between scientists from these various disciplines-vital to the advancement of our understanding of the function of the nervous system-has become more and more difficult in recent years. Both increasing specialization and the incredible increases in publications pertinent to brain research in a wide spectrum of journals, in symposium volumes, in monographs, in abstracts, and in reviews contrib ute to the problems of cross-communication and even of communication within a scientific discipline. Research on the significance of cyclic nucleo tides to the function of nervous systems is particularly illustrative of the communication problem. Since the initial publications by Sutherland, Rall, and Butcher in the late fifties and early sixties on high levels of adenylate cyclase, phosphodiesterases, and cyclic AMP in brain, the ensuing litera ture of this field has expanded exponentially. At the present time, from five to ten publications relevant to cyclic nucleotides and the nervous system appear each week. Indeed, these are minimal numbers based mainly on examination of literature titles and key index words. Many articles concerned with some aspect of central function contain, buried within their text, experiments with or related to cyclic nucleotides.

This book reviews advances in understanding phosphodiesterases within the central nervous system and their therapeutic applications. A range of expert authors from both academia and industry describe these, then focus on the areas of greatest scientific and medical interest to provide more detailed coverage. Therapeutic and drug discovery applications are covered for diseases including Alzheimer's, Parkinson's, schizophrenia, erectile dysfunction, and spinal cord injuries. There is also a chapter on drug discovery tools such as in vitro assays and X-ray structures for medicinal chemistry studies.

Cyclic nucleotides are intimately involved in the consequences of either stimulation or blockade of receptors; therefore, an understanding of the biochemistry of cyclic nucleotides ought to be important for pharmacologists. Pharmacology is a science that among other things investigates chemical compounds that affect the physiology of cells, tissues and organs. Frequently pharmacologists account for the effect of low concentrations of a drug upon a tissue by invoking the presence of a receptor upon the surface of the cell. Traditional pharmacologists excelled at identifying and classifying the properties of receptors. A. J. CLARK'S monograph in the earlier series of the Handbook of Experimental Pharmacology (CLARK 1937) summarized the mathematics underlying the traditional pharmacological approach towards receptors. By its nature, however, classic pharmacology provided little useful information about the intracellular events occurring as a consequence of occupying a receptor; for example, ALQUIST (1948) identified the beta-adrenocep tor, but he did not provide any insight into how stimulation of the receptor produces tissue-specific physiological responses. The discovery of cyclic AMP by RALL and SUTHERLAND (see RALL, Vol. I) led to biochemical investigations of many different receptors (including ALQUIST'S beta-adrenoceptor) that share a cyclic nucleotide as a common factor in the biochemical mechanisms that translate the occupancy of receptors into physiological effects. Ten years ago, in the introduction to their monograph on cyclic nucleotides, ROBISON et al. (1971) commented on the rapid growth of interest in cyclic nucleotides over the preceding years.

The purpose of the present volume, the first of two on the pharmacology, biochemistry, and physiology of cyclic nucleotides, is to provide a comprehensive and up-to-date anthology on the nature and role of these important chemical regulators. Each of the chapters is the work of internationally known researchers who present a lucid and detailed review of their subject and not merely a single laboratory's viewpoint. The chapters emphasize critical assessments of the field rather than mere listings of experimental findings. By so doing, the contributors present the role of cyclic nucleotides in relationship to other intracellular regulators. Each chapter begins with a detailed summary to allow the reader to obtain a rapid overview of subsequent material. In addition, there are extensive bibliographies and a detailed subject index. Wherever pertinent, the chapters contain sections on drug mechanisms, physiological relevance, and disease processes. The Volume is divided into two sections, each beginning with an overview written by Professors T. W. RALL and P. GREENGARD, respectively. The first section focuses on the detailed pharmacology and chemistry of cyclic nucleotides, including their formation, degradation, measurement, and interaction with various modulatory agents, such as receptors and calcium. The second section is concerned with the biochemistry of protein phosphorylation, a process which appears to be one of the most important mechanisms for the intracellular expression of cyclic nucleotide action in eukaryotic cells.

Volume 54, Symposium S7: Cyclic Nucleotides and Protein Phosphorylation in Cell Regulation documents the proceedings of the 12th Federation of European Biochemical Societies (FEBS) Meeting held in Dresden, Germany on July 5-7, 1978. This book discusses the biological significance and biochemical aspects of cyclic nucleotides and protein phosphorylation in cell regulation. The general aspects of cyclic nucleotide metabolism and action; cyclic nucleotides and nervous system; and cyclic nucleotides in muscle tissues are also elaborated. This publication likewise covers the cyclic nucleotides in secretion processes and miscellaneous aspects of cyclic nucleotide-dependent and independent protein phosphorylation. This volume is valuable to biochemists and biologists concerned with the cyclic nucleotides and protein phosphorylation in cell regulation.

Advances in Pharmacology and Therapeutics, Volume 3: Ions – Cyclic Nucleotides – Cholinergy covers the proceedings of the Seventh International Congress of Pharmacology, held in Paris in 1978. This book mainly focuses on studying ions, cyclic nucleotides, and cholinergy. Specifically, this text discusses the pharmacology of calcium homeostasis and presents lectures given in the symposium. The role of cyclic nucleotides in the regulation of muscular tissue functions and the evaluation of cyclic AMP and cyclic GMP are also looked into. This text presents in its latter part papers on chemical structure and cholinergic activity. This volume will be valuable to students and experts in the field of pharmacology, therapeutics, and related fields.

Cyclic nucleotides control a number of neuronal properties including neuronal differentiation, pathfinding, regulation of excitability and synaptic transmission, and control of gene expression. Signaling events mediated by cAMP or cGMP are transient and take place within the complex 3-dimensional structure of the neuronal cell. Signaling events happen on the time scale of seconds to minutes and the biological significance of the temporal dimension remains poorly understood. Structural features of neurons (dendritic spines and branches, cell body, nucleus, axon…) as well as AKAPs and other scaffolding proteins that keep signaling enzymes together and form "signaling microdomains", are critical spatial determinants of signal integration. Finally, the types of enzymes involved in signal integration, which are expressed as a number of different types and splice variants, yield another dimension that determines signal integration properties. Biosensor imaging provides direct temporal and spatial measurement of intracellular signals. This novel approach, together with more conventional methods such as biochemistry, electrophysiology, and modeling, now provide a better understanding of the spatial and temporal features of cyclic nucleotide signal integration in living neurons. This topic aims at providing a better understanding of how neurons are "making sense" of cyclic nucleotide signaling in living neurons.

Biochemical Correlates of Brain Structure and Function deals with the biochemical correlates of brain structure and function, providing some examples of contemporary work interrelating structure with function of the nervous system. The developing brain provides a system for this kind of study, but broad correlates are also drawn between changing biochemistry and increasing physiological activity. This book is organized into nine chapters and begins with an overview of biochemical, morphological, and functional changes in the developing brain, as well as the underlying molecular basis of nerve differentiation and growth of the developing brain. An account of the concept of the cell cycle and its control is also given. The reader is methodically introduced to the properties of the developing retina and its functional biochemistry, with specific reference to the cyclic nucleotides; the use of selective lesioning to delineate GABA-ergic and cholinergic tracts as well as the catecholamine pathways; and cerebral blood flow alteration in concert with mental activity. The remaining chapters explore regions of the brain with altered glucose utilization in response to changes in local functional activity; the physiologically important factors regulating the supply of oxygen and glucose and the relation of metabolic rate to the metabolic state of the brain; and varying aspects of behavioral neurochemistry. This book is intended for chemists and biologists as well as students of biochemistry.

Since the last major compendium dedicated to cyclic nucleotide phosphodiesterases (PDEs) was published over 15 years ago, an enormous amount of progress has occurred in the field. There is great need for a centralized source for key information in this burgeoning and therapeutically important area of medical research. Cyclic Nucleotide Phosph