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. The number of identified PDEs has doubled, their roles in intracellular communication have begun to be understood, and several PDE inhibitors have entered the pharmaceutical market with huge commercial success. There is great need for a centralized source for key information in this burgeoning and therapeutically important area of medical research. "Cyclic Nucleotide Phosphodiesterases in Health and Disease" provides an integrated volume covering PDE biology from genes to organisms. It examines phosphodiesterases as pharmacological targets as well as the development of specific PDE inhibitors as therapeutic agents. With contributions from pioneers in the field, individual chapters describe one of the 11 known mammalian PDE families including the molecular characteristics, structure, function, and traits unique to each.
Characteristics of PDEs from lower organisms are also the subject of other chapters since they provide key insights into PDE functions and are also pharmacological targets for treatment of a variety of diseases in humans and domestic animals. Chapters on the current biomedical and therapeutic research on PDEs include studies on gene-targeted knockout strategies and compartmentation in cyclic nucleotide signaling. By unraveling the unique cellular roles for different PDEs, scientists are beginning to open the door to the therapeutic use of PDE inhibitors for the treatment of a number of pathological conditions including asthma and inflammation, pulmonary hypertension, erectile dysfunction, and stroke. By collating current information into a coherent and coordinated perspective, "Cyclic Nucleotide Phosphodiesterases in Health and Disease" provides an invaluable reference for industry and clinical scientists and points toward future directions of research and therapeutic advancements in developing selective inhibitors for these various enzymes.
Cyclic Nucleotide Phosphodiesterase Superfamily, J. A. Beavo, M. D. Houslay, and S. H. Francis Phosphodiesterase Isoforms-An Annotated List, G. B. Bolger Section A Specific Phosphodiesterase Families-Regulation, Molecular and Biochemical Characteristics Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterases, A. T. Bender PDE2 Structure and Functions, S. E. Martinez Phosphodiesterase 3B: An Important Regulator of Energy Homeostasis, E. Degerman and V. Manganiello Cellular Functions of PDE4 Enzymes, G. B. Bolger, M. Conti, and M. D. Houslay Phosphodiesterase 5: Molecular Characteristics Relating to Structure, Function, and Regulation, S. H. Francis, R. Zoraghi, J. Kotera, H. Ke, E. P. Bessay, M. A. Blount, and J. D. Corbin Photoreceptor Phosphodiesterase (PDE6): A G-Protein-Activated PDE Regulating Visual Excitation in Rod and Cone Photoreceptor Cells, R. H. Cote PDE7, T. Michaeli cAMP-Phosphodiesterase PDE 8 , V. Vasta PDE9, J. Kotera and K. Omori PDE10A: A Striatum Enriched, Dual-Substrate Phosphodiesterase, C. A. Strick, C. J. Schmidt, and F. S. Menniti PDE11, K. Omori and J. Kotera Section B Nonmammalian Phosphodiesterases Protozoal Phosphodiesterases, L.Wentzinger and T. Seebeck Studies of Phosphodiesterase Function Using Fruit Fly Genomics and Transgenics, S. A. Davies and J. P. Day Section C Phosphodiesterases Functional Significance: Gene-Targeted Knockout Strategies Insights into the Physiological Functions of PDE4 from Knockout Mice, S. L. C. Jin, W. Richter, and M. Conti Regulation of cAMP Level by PDE3B-Physiological Implications in Energy Balance and Insulin Secretion, A. Z. Zhao and L. Stenson Holst Section D Compartmentation in Cyclic Nucleotide Signaling Heart Failure, Fibrosis, and Cyclic Nucleotide Metabolism in Cardiac Fibroblasts, S. A. Epperson and L. L. Brunton Role of A-Kinase Anchoring Proteins in the Compartmentation in Cyclic Nucleotide Signaling, O. Witczak, E. M. Aandahl, and K. Tasken Role of Phosphodiesterases in Cyclic Nucleotide Compartmentation in Cardiac Myocytes, A. Abi-Gerges, L. R.V. Castro, F. Rochais, G. Vandecasteele, and R. Fischmeister Section E Phosphodiesterases as Pharmacological Targets in Disease Processes Role of PDEs in Vascular Health and Disease: Endothelial PDEs and Angiogenesis, T. Keravis, A. P. Silva, L. Favot, and C. Lugnier Regulation of PDE Expression in Arteries: Role in Controlling Vascular Cyclic Nucleotide Signaling, D. H. Maurice and D. G. Tilley Regulation and Function of Cyclic Nucleotide Phosphodiesterases in Vascular Smooth Muscle and Vascular Diseases, C. Yan, D. J. Nagel, and K. Jeon Role of Cyclic Nucleotide Phosphodiesterases in Heart Failure and Hypertension, M. A. Movsesian and C. J. Smith Molecular Determinants in Pulmonary Hypertension: The Role of PDE5, N.J. Pyne, F. Murray, R. Tate, and M.R. MacLean Role of PDE5 in Migraine, C. Kruuse Phosphodiesterase-4 as a Pharmacological Target Mediating Antidepressant and Cognitive Effects on Behavior, H. T. Zhang and J. M. O'Donnell Role of Phosphodiesterases in Apoptosis, A. Lerner, E. Y.Moon, and S. Tiwari Section F Development of Specific Phosphodiesterase Inhibitors as Therapeutic Agents Crystal Structure of Phosphodiesterase Families and the Potential for Rational Drug Design, K. Y. J. Zhang Structure, Catalytic Mechanism, and Inhibitor Selectivity of Cyclic Nucleotide Phosphodiesterases, H. Ke and H. Wang Bench to Bedside: Multiple Actions of the PDE3 Inhibitor Cilostazol, J. Kambayashi, Y. Shakur, and Y. Liu Reinventing the Wheel: Nonselective Phosphodiesterase Inhibitors for Chronic Inflammatory Diseases, M. A. Giembycz Medicinal Chemistry of PDE4 Inhibitors, J. M. McKenna and G. W. Muller Index