Calcium in Drug Actions by Peter F. BakerCalcium in Drug Actions by Peter F. Baker

Calcium in Drug Actions

byPeter F. Baker

Paperback | December 13, 2011

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The Editorial Board and the Publishers of the Handbook of Experimental Pharmacology wish to express their profound grief at the untimely death of Professor Peter Baker. Aware of his international recognition as an expert on the ubiquitous role of calcium in physiological processes and their pharma­ cological control, the Board was gratified when Professor Baker accepted its invitation to edit a new Handbook volume on "Calcium in Drug Actions". He went about this task with his usual energy and effectiveness so that, in the few months before his unexpected death, Professor Baker had mustered his distinguished contributors, got them to provide their manuscripts, and seen almost the entire material into the press. This achievement is all the more remarkable when one bears in mind the extraordinary number of his other commitments during the same time; they are mentioned in Sir Alan Hodgkin's preface to this volume. With so many other professional and personal responsibilities upon him, the Board of the Handbook wishes to record its grateful appreciation for the admirable way in which Professor Baker took on and carried out the additional work of bringing this fine book into existence; and the Board wishes it to be dedicated to the memory of Professor Peter Frederick Baker. The Editorial Board: G. V. R. BORN, P. CUATRECASAS, H. HERKEN, A.
Title:Calcium in Drug ActionsFormat:PaperbackDimensions:567 pages, 24.2 × 17 × 0.07 inPublished:December 13, 2011Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:3642718086

ISBN - 13:9783642718083

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Table of Contents

1 The Multiple Physiological Roles of Calcium: Possible Sites for Pharmacological Intervention.- References.- Calcium Receptors and Calcium Metabolism.- 2 Chemical Factors Determining the Affinity of a Receptor for Calcium.- A. Introduction.- B. Concentrations in Physiological Conditions.- C. Calcium-Proton Competition.- D. The Calcium-Magnesium Problem.- E. Other Metal Ions.- F. Cooperative Interactions.- G. Binding and Conformational Energy.- H. Kinetic Constraints.- J. On-Off Binding Constants.- K. Diffusion of Ions.- I. In Water.- II. Through Membranes.- III. Pumps.- L. Selective Binding to Unstructured Molecules of High Anionic Charge Density.- M. The Function of Neutral Donors.- N. Calmodulin: An Example of a Calcium Trigger.- O. S-100b: An Example of Ion-Ion Cooperativity.- P. A Look at Phosphorylation Regulation.- Q. Conclusion.- References.- 3 Troponin C and Calmodulin as Calcium Receptors: Mode of Action and Sensitivity to Drugs.- A. Introduction.- B. Brief Historical Survey of Ca Receptor Proteins.- C. General Views of TNC and CaM.- D. Ca Binding of TNC and CaM.- E. Ca Binding to TNC in Relation to Tension Development.- F. Ca Binding to CaM and Enzyme Activities.- G. CaM Ligands: Their Pharmacologic and Physiologic Significance..- I. Discovery of CaM-Inhibiting Drugs (CaM Antagonists).- II. CaM Ligands.- H. Concluding Remarks.- References.- 4 Ligand-Binding Sites on Calmodulin.- A. Introduction.- B. Metal Ion-Binding Sites.- I. Calcium.- II. Calcium Probe Cations.- III. Other Metal Ions.- C. Binding of Drugs.- I. Trifluoperazine.- II. Calmodulin Antagonists.- III. Calcium Antagonists.- D. Binding of Peptides.- I. Structural Requirements.- II. Localization of Binding Sites.- E. Interactions with Target Proteins.- I. Chemical Modifications and Affinity Labeling.- II. Activation and Binding with Calmodulin Fragments.- III. Calmodulin-Binding Domains.- F. Epilogue.- References.- 5 Calcium Channels as Drug Receptors.- A. Introduction.- B. Calcium as a Biological Signalling Mechanism and the Role of Calcium Channels in Maintaining Its Homeostasis.- C. How Many Types of Calcium Channels Exist?.- D. Electrophysiological Properties of the Calcium Channel.- E. Physiological Modulation of Calcium Channel Function.- F. Calcium Antagonists.- G. The 1,4-Dihydropyridine Receptor.- H. Calcium Agonists.- J. Summary and Conclusions.- References.- 6 The Chemistry of Calcium Channel Agonists and Antagonists.- A. Introduction.- B. Structure-Function Studies.- C. Binding Sites for Ca2 + Channel Ligands.- D. Ca2+ Channel Binding Sites: Relationship to Ca2+ Channel Function..- E. Relationship of Structural and Functional Studies: A Prospective.- I. Different Categories of Ca2+ Channels.- II. State-Dependent Interactions with Ca2 + Channels.- III. Pathologic State of Tissue.- References.- 7 The Apamin-Sensitive Ca2+-Dependent K+ Channel: Molecular Properties, Differentiation, Involvement in Muscle Disease, and Endogenous Ligands in Mammalian Brain.- A. Apamin, Its Structure and Its Active Site.- B. Apamin Blocks Ca2+-Dependent K+ Channels.- C. The Apamin-Sensitive Ca2+-Dependent K+ Channel is Only One of Several Types of Ca2+-Dependent K+ Channels.- D. Biochemical Properties of the Apamin-Binding Component of the Ca2+-Dependent K+ Conductance.- E. Apamin as a Tool to Purify the Apamin-Sensitive Ca2+-Dependent K+ Channel and to Determine Its Molecular Weight and Its Polypeptide Composition.- F. PCI2 Pheochromocytoma Cells Hyperproduce the Apamin Receptor and Permit an Analysis of the Internal Ca2+ Concentration Dependence of the Apamin-Sensitive Ca2 + Channel.- G. Autoradiographic Localization of Apamin-Sensitive Ca2+-Dependent K+ Channels in Rat Brain.- H. Developmental Properties of the Ca2+-Dependent K+ Channel in Mammalian Skeletal Muscle and the All-or-None Role of Innervation.- I. Expression of the Apamin Receptor in Muscles of Patients with Myotonic Muscular Dystrophy.- J. An Endogenous Apamin-Like Factor Modulating Ca2+-Dependent K+ Channel Activity Exists in Mammalian Brain.- References.- 8 Drug Effects on Plasma Membrane Calcium Transport.- A. Introduction.- B. Calmodulin.- C. Calmodulin-Binding Site.- D. ATPase Catalytic Unit.- E. Phospholipid Environment.- F. Influx Pathways.- G. Surface Receptors.- H. Summary.- References.- 9 Development of Inhibitors of Sodium, Calcium Exchange.- A. Introduction.- B. Characteristics and Physiologic Properties of Na,Ca Exchange.- C. Identification of Na,Ca Exchange Inhibitors.- D. Mechanism of Na,Ca Exchange Inhibition by Amiloride and Bepridil.- E. Pharmacology of Na,Ca Exchange Inhibitors.- References.- 10 The Effect of Ruthenium Red and Other Agents on Mitochondrial Calcium Metabolism.- A. Introduction.- B. Inhibitors of the Mitochondrial Ca2 + Transport Systems.- I. Ruthenium Red.- II. Benzothiazepines.- III. Other Ca2 + Antagonists.- IV. Benzodiazepines.- V. Trifluoperazine.- VI. Gentamicin.- VII. Amiloride Analogues.- C. Effectors of Ca2+-Induced Permeabilization.- D. Mitochondrial Ca2+ Overload.- I. Mitochondrial Ca2+ and Oxidative Phosphorylation During Ischaemia/Reperfusion.- II. The Effects of Ruthenium Red and Other Agents on Mitochondrial Ca2 +.- References.- 11 Pharmacology of Calcium Uptake and Release from the Sarcoplasmic Reticulum: Sensitivity to Methylxanthines and Ryanodine.- A. Introduction.- B. Methylxanthines.- I. The Effect of Caffeine on Ca Uptake.- II. The Release of Ca from the Sarcoplasmic Reticulum by Caffeine.- III. The Effect of Caffeine on the Passive Efflux of Ca.- IV. The Effect of Caffeine on Ca,Mg-ATPase Activity.- V. Heavy and Light Fractions of Isolated Sarcoplasmic Reticulum.- VI. Structure-Activity Relations for the Methylxanthines.- C. Ryanodine.- D. Conclusions.- References.- 12 Effect of Lithium in Stimulus-Response Coupling.- A. Introduction.- B. Lithium.- C. Phosphoinositides and Calcium.- D. A Link Between Lithium, Phospholipids and Ca2+ Mobilization.- E. Inositol-1,4,5-Trisphosphate as Second Messenger in the Action of Ca2+-Mobilizing Hormones.- F. Other Inositol Polyphosphates.- G. Lithium and Manic-Depressive Illness.- H. Is Lithium a Secretagogue?.- J. A Link Between Li+, Phosphoinositides and Cell Proliferation.- K. Effects of Li+ on Neurotransmitter-cAMP-Stimulated Pathways.- L. Conclusion.- References.- 13 Phorbol Esters and Protein Kinase C.- A. Introduction.- B. Purification and Assay of Protein Kinase C.- I. Purification of Protein Kinase C from Rat Brain.- II. Enzyme Assay of Protein Kinase C.- III. Binding Assay of Protein Kinase C.- C. Protein Kinase C and Phorbol Esters.- I. Properties.- II. Biochemical and Physiologic Activation.- III. Permeable Diacylglycerol and Phorbol Esters.- D. Conclusion.- References.- Calcium and Physiological Function.- 14 Drugs Acting on Calcium Channels.- A. Introduction.- B. Methods.- I. Materials.- II. Electrical Recording.- III. Solutions.- C. Two Types of Calcium Channels.- I. Initial Study.- II. Separation of Two Types of Calcium Channels.- III. Kinetics of Two Types of Calcium Channels.- IV. Ionic Selectivity.- V. Sensitivity to Cyclic AMP.- D. Pharmacology of Calcium Channels.- I. Polyvalent Cations.- II. Opioid Peptides.- III. Phenytoin.- IV. Pyrethroids.- E. Summary and Conclusions.- References.- 15 Calcium and Synaptic Function.- A. Introduction.- B. Regulation of Intracellular Calcium in Nerve Cells.- I. The Intracellular Free Calcium Concentration in Nerve Cells.- II. Calcium Entry into Nerve Cells.- III. Intracellular Calcium Buffering in Nerve Cells.- 1. Mitochondria.- 2. Smooth Endoplasmic Reticulum.- 3. Cytosolic Buffers.- IV. Calcium Transport Across the Neuronal Plasma Membrane.- V. The "Life Cycle" of Calcium at the Nerve Terminal.- C. The Role of Intracellular Calcium in Synaptic Transmission.- I. Calcium and Neurotransmitter Release.- II. Dissection of the Steps in Transmitter Release with Toxins and Drugs.- III. Calcium and the Control of Excitability in Neurons.- IV. Calcium and Memory.- D. Summary and Conclusions.- References.- 16 Some New Questions Concerning the Role of Ca2 + in Exocytosis.- A. Calcium and Cell Activation.- B. Exocytosis as an Example of a Cellular Activation Process.- I. Adrenal Chromaffin Cells.- II. Neutrophils.- III. The Mast Cells.- C. Direct Manipulation of Cytosol Ca2 +.- I. Calcium Ionophores.- II. Manipulation of Cytosol Ca2+ in Permeabilised Cells.- III. Methods of Plasma Membrane Permeabilisation.- IV. Ca2+-Induced Secretion from Permeabilised Neutrophils.- V. Ca2+-Induced Secretion from Permeabilised Adrenal Chromaffin Cells.- D. Exocytotic Secretion Without Elevation of Cytosol Ca2 +.- I. Phorbol Ester.- II. Guanine Nucleotides.- E. A Role for G-Protein in Exocytosis?.- F. Questions Concerning the Role of Ca2+ in Exocytosis.- I. Single Cells.- 1. Membrane Capacitance Changes in Exocytosis.- 2. Fast Ca2+ Transients Are not Sufficient to Trigger Exocytosis..- G. Towards Reconstitution of Exocytosis in Cell-Free Systems.- References.- 17 Exo-Endocytosis: Mechanisms of Drug and Toxin Action.- A. Introduction.- B. Exocytosis.- I. Second Messenger Control of Regulated Exocytosis.- II. Membrane Fusion-Fission in Exocytosis.- III. Drugs.- IV. Toxins.- 1. Toxins Targeted to Channels and Receptors.- 2. Clostridium Toxins: Inhibitors of Exocytosis.- 3. ?-Latrotoxin and Congeners: Stimulators of Exocytosis.- C. Endocytosis.- I. Membrane Sorting in Endocytosis.- II. Regulation of Endocytosis.- References.- 18 Pharmacology of Calcium Metabolism in Smooth Muscle.- A. Introduction.- B. Calcium Entry and Calcium Regulation at Rest: Action of Pharmacologic Agents.- C. Calcium Movements During Excitation: Their Sensitivity to Pharmacologic Agents.- D. Heterogeneity of Excitation-Contraction Coupling Mechanisms.- E. A Pharmacologic Example: Contraction of Vascular Smooth Muscle, Role of Endothelium, and Action of Dihydropyridines and Diphenylpiperazines.- I. Inhibition of Contraction.- II. Role of Endothelium.- F. Concluding Remarks.- References.- 19 Drugs Affecting Cardiac Calcium Metabolism.- A. Introduction.- B. The Calcium Signal.- C. Classification and Selection of Drugs.- D. Drugs Affecting Sarcolemmal Calcium-Transporting Proteins.- I. Calcium Channels.- 1. Direct Inhibitors and Activators: "Calcium Antagonists" and "Calcium Agonists".- 2. Drugs Acting via Cyclic AMP.- 3. Other Drugs.- II. Sodium/Calcium Exchange.- 1. Direct Inhibitors.- 2. Drugs Affecting Intracellular Sodium.- E. Drugs Affecting Sarcoreticular Calcium-Transporting Proteins.- F. Drugs Affecting Mitochondrial Calcium-Transporting Proteins.- G. Conclusions.- References.- 20 Hormonal Control of Extracellular Calcium.- A. Introduction.- B. Parathyroid Hormone.- I. Chemistry.- II. Biosynthesis.- III. Secretion and Metabolism.- IV. Biological Actions.- V. Pathophysiology.- 1. Primary Hyperparathyroidism.- 2. Renal Failure.- C. Hormone from the Corpuscle of Stannius.- I. Chemistry and Biosynthesis.- II. Biological Action.- D. Vitamin D: Endocrine System.- I. Chemistry and Biosynthesis.- II. Metabolism.- 1. Mineral Regulation.- 2. Hormonal Regulation.- a) Parathyroid Hormone.- b) Growth Hormone and Prolactin.- c) Calcitonin.- d) Vitamin D Metabolites.- III. Biological Actions.- IV. Pathophysiology.- E. The Calcitonin Gene Peptides.- I. Discovery.- 1. Calcitonin.- 2. Katacalcin.- 3. Calcitonin Gene-Related Peptide.- II. Biosynthesis.- III. Chemistry.- IV. Secretion.- V. Actions.- 1. Calcitonin.- 2. Calcitonin Gene-Related Peptide.- VI. Physiological Role.- 1. Calcitonin.- 2. Calcitonin Gene-Related Peptide.- VII. Pathophysiology: Medullary Carcinoma of the Thyroid.- VIII. Therapeutic Considerations.- 1. Calcitonin.- a) Paget's Disease.- b) Osteoporosis.- c) Hypercalcaemia.- 2. Calcitonin Gene-Related Peptide.- References.- 21 Bisphosphonates: A New Class of Drugs in Diseases of Bone and Calcium Metabolism.- A. Introduction.- B. Chemistry and General Characteristics.- C. Synthesis.- D. Methods of Determination.- E. Monophosphonates.- F. History.- G. Mode of Action.- I. Physicochemical Effects.- II. Effect on Calcification In Vivo.- III. Inhibition of Bone Resorption.- IV. Biochemical and Cellular Effects.- V. Mode of Action in the Inhibition of Bone Resorption.- VI. Other Effects.- H. Pharmacokinetics.- J. Toxicology.- K. Drug Interactions.- L. Clinical Use.- I. Ectopic Calcification and Ossification.- 1. Soft Tissue Calcification.- 2. Urolithiasis.- 3. Dental Calculus.- 4. Fibrodysplasia Ossificans Progressiva.- 5. Other Heterotopic Ossifications.- II. Abnormally Increased Bone Resorption.- 1. Paget's Disease.- 2. Primary Hyperparathyroidism.- 3. Hypercalcemia of Malignancy and Tumoral Bone Destruction..- 4. Osteoporosis.- M. Side Effects.- N. Future Prospects.- References.- 22 Calcium and Hypertension.- A. Introduction.- B. Role of Ca2 + in Vascular Smooth Muscle Contraction.- C. Role of Altered Ca2 + Metabolism in Hypertension.- I. Human Studies.- II. The Spontaneously Hypertensive Rat.- III. Ca2+ Antagonists and Hypertension.- D. Role of Dietary Calcium in Hypertension.- I. Human Studies.- II. The Spontaneously Hypertensive Rat.- E. Postulated Mechanisms.- I. Effect of Dietary Calcium on Vascular Smooth Muscle.- II. Dietary Calcium and Phosphate Metabolism.- III. Dietary Calcium, Sodium Metabolism, and Fluid Balance.- IV. Dietary Calcium and the Autonomic Nervous System.- V. Composite Hypothesis.- F. Conclusions.- References.- Drugs and Toxicological Agents that Either Mimic Calcium or Elements of Intracellular Calcium Metabolism.- 23 Calcium Chelators and Calcium Ionophores.- A. Introduction.- B. Calcium Chelators.- I. EGTA.- II. Carboxylate Ca2+ Chelators and Fluorescent Ca2+ Probes.- III. Metallochromic Dyes.- IV. Photoproteins.- C. Calcium Ionophores.- I. Naturally Occurring Calcium Ionophores.- 1. X-537A.- 2. A23187.- 3. Ionomycin.- II. Synthetically Produced Calcium Ionophores.- 1. DDP- and DOPP-.- 2. ETH 1001.- D. Conclusion.- References.- 24 Lead-Calcium Interactions and Lead Toxicity.- A. Overview.- B. Relevant Chemistry of Lead and Calcium.- I. Introduction.- II. Chemistry of the Ions in Solution.- 1. Complexes with Simple Anions.- 2. Complexes with Organic Ligands.- 3. Ionic Radius.- III. Measurement of Pb2+ Concentration.- IV. Pb2+ Buffers.- C. Nonenzymic Actions of Lead.- D. Interactions Between Lead and Binding Proteins.- I. Calmodulin.- II. Troponin C.- III. Intestinal Calcium-Binding Proteins.- IV. Lead-Binding Proteins.- V. Summary.- E. Lead-Enzyme Interactions.- I. Ca2+-ATPase.- II. ?-Aminolevulinic Acid Dehydratase.- III. Adenylate Cyclase.- IV. Na+, K+-ATPase.- V. Calmodulin-Dependent Actions.- VI. Summary.- F. Transport of Lead, and Its Effects Upon Ion Transport.- I. Transport Across the Plasma Membrane.- 1. Human Red Blood Cells.- 2. Ca Channels.- II. Transport Across Epithelia.- 1. Intestinal Absorption.- 2. Renal Absorption and Excretion.- III. Mitochondria.- G. Cellular Homeostasis.- H. Neurotransmission and Neurosecretion.- J. Summary and Conclusions.- References.- 25 Alkaline Earths, Transition Metals, and Lanthanides.- A. Introduction.- B. Interactions of Alkaline Earths, Transition Metals, and Lanthanides with Calcium Channels.- I. Slow, Voltage-Operated Calcium Channels.- II. Other Types of Calcium Transport Mechanisms.- C. Cellular Physiologic Effects of Inorganic Blockers of Calcium Channels.- D. Metal Ions as Drugs.- E. Metabolism of Lanthanides by Whole Animals.- F. Possible Therapeutic Uses of the Lanthanides.- G. Summary.- References.