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After the discovery of endogenous NO formation in the late '80s and the 1998 Nobel Prize in Physiology or Medicine, many researchers and physicians again became interested in the NO/sGC interaction and cGMP-dependent signaling. This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. It is exclusively devoted to this exciting and important signaling molecule, addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. Particular attention will also be given to clinical applications of the novel cGMP-elevating drugs which are on the horizon, thus spanning the continuum from basic science to clinic.

cGMP: Generators, Effectors and Therapeutic Implications

Basic Generators and Effectors.- A Short History of cGMP, Guanylyl Cyclases, and cGMP-Dependent Protein Kinases.- Biochemistry of Soluble Guanylate Cyclase.- Genetic Mouse Models of the NO Receptor 'Soluble' Guanylyl Cyclases.- Function and Dysfunction of Mammalian Membrane Guanylyl Cyclase Receptors: Lessons from Genetic Mouse Models and Implications for Human Diseases.- Phosphodiesterases in the Central Nervous System.- Structural and Biochemical Aspects of Tandem GAF Domains.- Cyclic Nucleotide-Gated Channels.- cGMP Regulated Protein Kinases (cGK).- cGK Substrates.- Biochemical Detection of cGMP From Past to Present: An Overview.- Novel Techniques for Real-Time Monitoring of cGMP in Living Cells.- Pharmacology of cGMP.- NO and sGC-Stimulating NO Donors.- NO-Independent, Haem-Dependent Soluble Guanylate Cyclase Stimulators.- NO- and Haem-Independent Soluble Guanylate Cyclase Activators.- Natriuretic Peptides: Their Structures, Receptors, Physiologic Functions and Therapeutic Applications.- Cyclic GMP-Hydrolyzing Phosphodiesterases.- cGMP-Dependent Protein Kinase Modulators.- cGMP-Dependent Protein Kinase as a Modifier of Behaviour.- Clinical Applications.- cGMP in the Vasculature.- Modulating cGMP to Treat Lung Diseases.- Modulation of cGMP in Heart Failure: A New Therapeutic Paradigm.- Erectile Dysfunction and Lower Urinary Tract.- cGMP and cGMP-Dependent Protein Kinase in Platelets and Blood Cells.- cGMP Signalling in the Mammalian Brain: Role in Synaptic Plasticity and Behaviour.