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Preface; Contents; Part I: Cyclic Nucleotide Microdomains; 1: Receptor-Cyclic Nucleotide Microdomains in the Heart; 1.1 Introduction; 1.2 Biosensors for cAMP and cGMP; 1.3 Mechanisms of Compartmentation in Microdomains; 1.4 Receptor-cAMP/cGMP Microdomain Visualization; References; 2: Membrane Microdomains and cAMP Compartmentation in Cardiac Myocytes; 2.1 Introduction; 2.2 Membrane Microdomains; 2.3 Receptor-Mediated Responses; 2.3.1 €1-Adrenergic Receptors (€1ARs); 2.3.2 €2-Adrenergic Receptors (€2ARs); 2.3.3 M2 Muscarinic Receptors (M2Rs); 2.3.4 Prostaglandin Receptors (EPRs).
5: Chatting Second Messengers: PIP3 and cAMP5.1 Introduction; 5.2 PIP3: A Signaling Lipid on Membranes; 5.3 Mechanisms of Cross-Talk between PIP3 and cAMP Signaling; 5.3.1 PIP3-Mediated Downregulation of €-AR/cAMP Signaling in Heart Failure; 5.3.2 PIP3- and PI3K-Dependent Control of cAMP Hydrolysis; 5.3.3 cAMP-Mediated Regulation of PIP3 Signaling; References; 6: Cyclic Nucleotide Phosphodiesterases and Compartmentation in Normal and Diseased Heart; 6.1 Introduction; 6.2 CN Signalling in Cardiac Myocytes; 6.3 Overview of the PDE Superfamily.
2.4 Conclusions and Future DirectionsReferences; 3: Function to Failure: Compartmentalization of Cardiomyocyte Signaling by A-Kinase-ƯAnchoring Proteins; 3.1 Introduction; 3.2 AKAPs and Regulation of the Calcium Cycle; 3.2.1 AKAP7 (Small Isoforms); 3.2.2 AKAP7 (Large); 3.2.3 AKAP5 (AKAP75/AKAP79/AKAP150); 3.3 AKAPs and Cardiac Remodeling; 3.3.1 AKAP6; 3.3.2 AKAP13; 3.4 Other AKAPs with Characterized Functions; References; 4: Pharmacological Approaches for Delineating Functions of AKAP-ƯBased Signalling Complexes and Finding Therapeutic Targets; 4.1 Introduction.
4.1.1 The cAMP Signalling Cascade4.1.2 cAMP Effectors; 4.1.3 cAMP Signalling Compartments; 4.2 A-Kinase Anchoring Proteins (AKAPs); 4.2.1 AKAP-PKA Interactions; 4.2.2 The Role of AKAPs in the Heart and Cardiovascular Diseases Exemplifies Their Potential Value as Drug Targets; 4.3 AKAP-PKA Disruptors; 4.3.1 Peptides; 4.3.1.1 Binding to R-Subunits of PKA; 4.3.1.2 Binding to AKB Domains of AKAPs; 4.3.1.3 Modified Peptides; 4.3.2 Peptidomimetics; 4.3.3 Small Molecules; 4.3.4 Disruptors of Interaction Between AKAPs and Proteins Other Than PKA; 4.4 Conclusions and Outlook; References.
6.4 Role of PDEs in Cyclic Nucleotide Compartmentation6.5 PDEs and Cyclic Nucleotide Compartmentation in Heart Failure; 6.6 PDEs as Therapeutic Targets in Ischemia/Reperfusion Injury?; 6.7 Concluding Remarks; References; 7: cAMP Compartmentalisation and Hypertrophy of the Heart: 'Good' Pools of cAMP and 'Bad' Pools of cAMP Coexist in the Same Cardiac Myocyte; 7.1 cAMP Signalling in the Heart; 7.2 Compartmentalisation of the cAMP Signalling Pathway; 7.3 Compartmentalisation of GPCRs and ACs; 7.4 PKA Compartmentalisation via AKAPs; 7.5 PDEs and cAMP Compartmentalisation.
5: Chatting Second Messengers: PIP3 and cAMP5.1 Introduction; 5.2 PIP3: A Signaling Lipid on Membranes; 5.3 Mechanisms of Cross-Talk between PIP3 and cAMP Signaling; 5.3.1 PIP3-Mediated Downregulation of €-AR/cAMP Signaling in Heart Failure; 5.3.2 PIP3- and PI3K-Dependent Control of cAMP Hydrolysis; 5.3.3 cAMP-Mediated Regulation of PIP3 Signaling; References; 6: Cyclic Nucleotide Phosphodiesterases and Compartmentation in Normal and Diseased Heart; 6.1 Introduction; 6.2 CN Signalling in Cardiac Myocytes; 6.3 Overview of the PDE Superfamily.
2.4 Conclusions and Future DirectionsReferences; 3: Function to Failure: Compartmentalization of Cardiomyocyte Signaling by A-Kinase-ƯAnchoring Proteins; 3.1 Introduction; 3.2 AKAPs and Regulation of the Calcium Cycle; 3.2.1 AKAP7 (Small Isoforms); 3.2.2 AKAP7 (Large); 3.2.3 AKAP5 (AKAP75/AKAP79/AKAP150); 3.3 AKAPs and Cardiac Remodeling; 3.3.1 AKAP6; 3.3.2 AKAP13; 3.4 Other AKAPs with Characterized Functions; References; 4: Pharmacological Approaches for Delineating Functions of AKAP-ƯBased Signalling Complexes and Finding Therapeutic Targets; 4.1 Introduction.
4.1.1 The cAMP Signalling Cascade4.1.2 cAMP Effectors; 4.1.3 cAMP Signalling Compartments; 4.2 A-Kinase Anchoring Proteins (AKAPs); 4.2.1 AKAP-PKA Interactions; 4.2.2 The Role of AKAPs in the Heart and Cardiovascular Diseases Exemplifies Their Potential Value as Drug Targets; 4.3 AKAP-PKA Disruptors; 4.3.1 Peptides; 4.3.1.1 Binding to R-Subunits of PKA; 4.3.1.2 Binding to AKB Domains of AKAPs; 4.3.1.3 Modified Peptides; 4.3.2 Peptidomimetics; 4.3.3 Small Molecules; 4.3.4 Disruptors of Interaction Between AKAPs and Proteins Other Than PKA; 4.4 Conclusions and Outlook; References.
6.4 Role of PDEs in Cyclic Nucleotide Compartmentation6.5 PDEs and Cyclic Nucleotide Compartmentation in Heart Failure; 6.6 PDEs as Therapeutic Targets in Ischemia/Reperfusion Injury?; 6.7 Concluding Remarks; References; 7: cAMP Compartmentalisation and Hypertrophy of the Heart: 'Good' Pools of cAMP and 'Bad' Pools of cAMP Coexist in the Same Cardiac Myocyte; 7.1 cAMP Signalling in the Heart; 7.2 Compartmentalisation of the cAMP Signalling Pathway; 7.3 Compartmentalisation of GPCRs and ACs; 7.4 PKA Compartmentalisation via AKAPs; 7.5 PDEs and cAMP Compartmentalisation.