Calcium in Drug Actions

Calcium in Drug Actions

by Peter F. Baker (Editor)

Paperback(Softcover reprint of the original 1st ed. 1988)

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Product Details

ISBN-13: 9783642718083
Publisher: Springer Berlin Heidelberg
Publication date: 12/13/2011
Series: Handbook of Experimental Pharmacology , #83
Edition description: Softcover reprint of the original 1st ed. 1988
Pages: 567
Product dimensions: 6.69(w) x 9.53(h) x 0.05(d)

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.

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