1st Edition
Cyclic Nucleotide Phosphodiesterases in Health and Disease
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 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.
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. Taskén
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
Biography
Joseph A. Beavo is a professor of pharmacology at the University of Washington. He obtained a BS from Stetson University in Deland, Florida and then a PhD from Vanderbilt University in Nashville, Tennessee. He has been involved in research concerning cyclic nucleotide phosphodiesterases since his graduate work with Drs. Joel Hardman and Earl Sutherland in the 1960s. He is an active member of the American Society for Pharmacology and Experimental Therapeutics and the National Academy of Sciences, having served on the editorial boards of journals published by both organizations. His current research focuses on the structural mechanisms of regulation of cyclic nucleotide phosphodiesterases and also on the functional roles played by the different phosphodiesterase gene products. Sharron H. Francis is a research professor of molecular physiology and biophysics at Vanderbilt University School of Medicine in Nashville, Tennessee. She obtained her undergraduate degree with emphasis in biology and chemistry from the Western Kentucky State in Bowling Green; studies for her doctoral degree in physiology were performed at Vanderbilt University under the guidance of Jane Park, PhD. She did postdoctoral study with Dr. Herman Eisen at Washington University in St. Louis, Missouri and was a research fellow in the Laboratory of Biochemistry at the National Heart and Lung Institute in Bethesda, Maryland under the guidance of Earl Stadtman, PhD. She is an active member of the American Society for Biochemistry and Molecular Biology, served the Scientific Advisory Board for Cell Pathways, Inc., and also has served as a consultant for numerous pharmaceutical companies. Her research interests focus on mechanisms involved in cGMP signaling, molecular characteristics of cGMP-dependent protein kinase, and phosphodiesterase-5, which are targets of cGMP, and the features that contribute to potent inhibition of phosphodiesterase- 5 by selective inhibitors. Miles D. Houslay is a Gardiner professor of biochemistry at the University of Glasgow, Scotland, UK. He obtained his first degree in biochemistry at the University of Wales in Cardiff and then his PhD from King’s College, Cambridge. He has held faculty positions at the Universities of Cambridge and Manchester. He is a fellow of the Royal Society of Edinburgh, Colworth Medal Holder of the British Biochemical Society, has served as member= chair of numerous grant agencies, and has consulted widely in the pharmaceutical industry. He has been involved in cell signaling research since its inception. His current research interest is focused on the role of phosphodiesterase-4 isoforms in underpinning cAMP compartmentalization and cross-talk processes and potential for identifying novel therapeutic opportunities.
