Contributors
Preface
Part I. Introduction
1. Calmodulin: An Introduction to Biochemical Aspects
I. History of Calmodulin
II. Physicochemical Properties
III. Distribution
IV. Functions of Calmodulin
V. Ca2+-Binding Properties
VI. Drug Binding to Calmodulin
References
2. Modulation of Ca2+-Dependent Regulatory Systems by Calmodulin Antagonists and Other Agents
I. Introduction
II. The Calcium Messenger System and Specific Inhibitors
III. Calcium Channel Blockers (Calcium Antagonists)
IV. Intracellular Calcium Antagonists
V. Calmodulin Antagonists
VI. Perspective
References
Part II. Mechanism of Action
3. The Interaction of Various Drugs with Calmodulin as Monitored by 113Cd NMR
I. Introduction
II. Experimental Details
III. Binding of Cations to Calmodulin
IV. Interaction of Various Drugs with Calmodulin
V. Conclusions and Further Studies
References
4. Calmodulin Antagonists: Structure-Activity Relationships
I. Introduction
II. Interaction of Phenothiazines with Calmodulin
III. Peptide Inhibitors of Calmodulin
IV. Other Types of Calmodulin Inhibitors
V. Agents that Act at Calmodulin-Binding Sites on Calmodulin-Sensitive Enzymes
VI. Conclusions
References
5. Structural Studies on Calmodulin and Troponin C: Phenothiazine, Peptide, and Protein Interactions with Calcium-Induced Helices
I. Introduction
II. EF Hand Structure
III. Calcium-Induced Helix
IV. Calcium-Induced Exposure of Hydrophobic Sites
V. Phenothiazine-Binding Sites and Specificity
VI. Location of Phenothiazine-Binding Sites
VII. Peptide Interactions
VIII. Protein Interactions
IX. Mechanism of Action of Troponin C and Calmodulin
X. Conclusions
References
Part III. Cell Proliferation and Growth
6. Effects of Calmodulin Antagonists on Cell Proliferation
I. Introduction
II. Effect of Calmodulin Antagonists on Growth of Cells in Culture
III. Calmodulin Levels in the Cell Division Cycle
IV. Effect of Calmodulin Levels on Actin-Containing Microfilaments
V. Conclusions
References
7. Potential Role of Calmodulin in Tumor Promotion: Modulator of Gap Junctional Intercellular Communication
I. Initiation and Promotion Concept of Carcinogenesis
II. Potential Role of Gap Junctional Intercellular Communication in Tumor Promotion
III. Role of Calcium in the Modulation of Gap Junctional Structure and Function
IV. Role of Calmodulin in the Modulation of Gap Junctional Structure and Function
V. Summary
References
8. Acrosome Reaction of Echinoderm Sperm
I. Introduction
II. Morphological Changes and Their Significance in Fertilization
III. Mechanism of the Acrosome Reaction
IV. The Acrosome Reaction and Calmodulin
V. Conclusion
References
9. The Role of Calmodulin in Oocyte Maturation
I. Introduction
II. Calmodulin and Calmodulin-Dependent Enzymes in Oocytes
III. Calmodulin Involvement in Oocyte Maturation
IV. Conclusion
References
Part IV. Cell Function
10. Neutrophil Activation and Calmodulin Antagonists
I. Introduction
II. The Presence of Calmodulin in Neutrophils
III. The Effect of Calmodulin Inhibitors on Neutrophil Function
IV. The Effect of Calmodulin Antagonists on Intracellular Biochemical Events Thought to be Related to Neutrophil Activation
V. Conclusions
References
11. The Role of Calmodulin in Sickle Cell Anemia
I. Introduction
II. Drugs Used for the Study
III. In Vitro Antisickling Effect of Various Drugs
IV. Formation and Inhibition of Irreversibly Sickled Cells
V. Possible Mechanism of Inhibition of the Formation of Dehydrated and Irreversibly Sickled Cells
VI. Importance of Dehydrated Cells and Irreversibly Sickled Cells in Sickle Cell Anemia
References
12. Thyroid Hormone and Calmodulin
I. Introduction
II. Thyroid Hormone Stimulation of Cell Membrane Ca2+-ATPase Activity
III. Calmodulin and Thyroid Hormone Action on Red Cell Ca2+-ATPase Activity
IV. Calmodulin and Thyroid Hormone Action on Membrane Transport of 2-Deoxy-D-Glucose
V. Other Interactions of Iodothyronines and Calmodulin
VI. Conclusions
References
Part V. Calmodulin and Contractile Process
13. The Phosphorylation of the 20,000-Dalton Myosin Light Chain in Intact Arterial Muscle
I. Introduction
II. Experimental Design
III. Results
IV. Discussion
V. Summary
References
14. Effects of Calmodulin Antagonists on Smooth Muscle Contraction and Myosin Phosphorylation
I. Introduction
II. Biochemical Properties of Myosin Phosphorylation
III. Physiological and Pharmacological Studies with Intact Smooth Muscle
References
15. Calmodulin Antagonists as Inhibitors of Platelet Aggregation and Secretion
I. Introduction
II. Role of Calmodulin in Platelet Aggregation and Secretion
III. Specificity of Calmodulin Antagonists
References
16. Actions of Felodipine in Vascular Smooth Muscle
I. Introduction
II. Effects on Smooth Muscle and Myocardial Contraction
III. Effects on 45Ca2+ Transport
IV. Intracellular Actions of Felodipine
V. Felodipine Binding to Calmodulin
VI. Effect of Felodipine on Calmodulin-Stimulated Enzymes
VII. General Discussion
References
17. Calcium-Dependent Protein Kinases and Calmodulin Antagonists
I. Introduction
II. Calcium—Calmodulin-Dependent Protein Kinases
III. Calcium—Phospholipid-Dependent Protein Kinase
IV. Inhibition of Calcium-Dependent Protein Phosphorylation by Calmodulin Antagonists
References
Part VI. Calmodulin and Related Membrane Function
18. Actions of Calmodulin and Cyclic Nucleotides in Vascular Smooth Muscles: Assessments from Drug Actions
I. Introduction
II. Recordings of Electrical and Mechanical Activities
III. Chlorpromazine Actions on Vascular Smooth Muscles
IV. Modulation of Calmodulin Action by Cyclic Nucleotides
V. Calmodulin Actions on Fragmented Membranes
VI. Conclusion
References
19. Interaction of Calmodulin Antagonists with Plasma Membrane and with Plasma Membrane Lipid
I. Introduction
II. Experimental Procedures
III. Monolayer Formation
IV. Drug Penetration of Membrane Lipid Monolayers
V. Interaction with Red Blood Cell Membranes
VI. Correlation of Calmodulin Inhibition with Different Physicochemical and Biochemical Drug Effects
VII. Conclusion
References
20. Ca2+-Pumping ATPase of Plasma Membranes
I. Introduction
II. Types of Enzymes Regulated by Calmodulin
III. Regulation of the Calcium2+ Pump by Calmodulin
IV. Regulation of the Calcium2+ Pump by Acidic Lipids and by Proteolysis
V. Calcium2+-Pumping ATPases from Plasma Membranes of Cell Types Other Than the Erythrocyte
VI. Effects of Calmodulin Antagonists on the Activity of Calcium2+-ATPase
VII. Summary
References
21. Effects of Calmodulin Antagonists on Ca2+-Transport ATPase
I. Introduction
II. Significance of Calcium -Transport ATPase
III. Potency of Calmodulin Antagonists
IV. Specificity of Calmodulin Antagonists
V. Mechanism of Action of Calmodulin Antagonists
VI. Summary and Conclusions
References
22. Contraction in Vas Deferens and Myometrium during Prolonged Exposure to Calcium-Free Solution
I. Introduction
II. Methods
III. Results
IV. Discussion
References
Part VII. Prostaglandin and Physiologically Active Substances
23. Roles for Phospholipase A2 and C in the Ca2+-CaM-Dependent Release of Arachidonate for Prostaglandin Synthesis in Inner Medulla
I. Introduction
II. Effects of Calmodulin Antagonists on Calcium-Induced Release of [14C]Arachidonate from Phospholipids of Renal Inner Medulla
III. Effects of Calmodulin Antagonists on Calcium-Induced Stimulation of Enzymes of the Phospholipase A2 and C Pathways
IV. Comments
References
24. Calmodulin and the Lung Arachidonic Acid System
I. The Lung as an Organ Regulated by Arachidonic Acid Metabolites
II. Calcium and Arachidonic Acid Cascade after Different Stimuli in Isolated Rabbit Lungs
III. Calcium and Arachidonic Acid Cascade after Different Stimuli in Cultured Pulmonary Endothelial Cells
IV. Calcium—Calmodulin: Common Link between Different Modes of Transmembrane Calcium Shift and Onset of the Arachidonic Acid Cascade in the Pulmonary Vascular Bed
References
25. Elucidation of Regulatory Mechanism of Tyrosine Hydroxylase and Tryptophan Hydroxylase by Calmodulin Antagonists
I. Introduction
II. Tyrosine Hydroxylase
III. Tryptophan Hydroxylase
IV. Conclusion
References
26. Calmodulin Antagonists and Vitamin D Metabolism
I. The Regulation of Vitamin D Metabolism in the Intact Organism
II. Regulation of 25(OH)D3 Metabolism to 1,25(OH)2D3 at the Cellular Level
References
Part VIII. Plant Calmodulin
27. Ca2+-Dependent Regulation of NAD Kinase and Protein Phosphorylation in Plants
I. Introduction
II. NAD Kinase
III. Regulation of Protein Phosphorylation
References
28. Intracellular Calcium Dynamics and Plant Cell Function
I. Introduction
II. Analysis of Intracellular Calcium Dynamics by Microscope Fluorometry
III. Pollen Germination and Pollen Tube Growth
IV. Intracellular Calcium, Cyclosis, and Chilling Stress
References
29. A Calmodulin and Calcium-Related Physiological Disorder (Bitter Pit) of Apples
I. Introduction
II. Materials and Methods
III. Results and Discussion
IV. Conclusion
References
Part IX. Applications of Calmodulin Antagonists
30. Calcimedins: Isolation Using Calmodulin Antagonists for Affinity Chromatography
I. Introduction
II. Calcium Dependency of Ligand Binding
III. Calcium-Binding Studies
IV. Regulation of Calcium Action
V. Conclusions
References
31. Immobilized Drugs in Protein and Peptide Isolation
I. Background
II. Antagonists Immobilized on Agarose
III. Antagonists Immobilized on Silica
IV. Summary
References
32. Interaction of W-7, a Calmodulin Antagonist, with Another Ca2+-Binding Protein
I. Introduction
II. Mechanism of Binding Affinity for Various Ca2+-Binding Proteins
III. Specific Interaction of S-100 Protein with W-7, a Calmodulin Antagonist
IV. Calmodulin Antagonists as a Tool for Research on S-100 Protein
V. Conclusions
References
33. Calmodulin Antagonists and Protein Kinase C
I. Calcium-Dependent Protein Kinases
II. Effect of Calmodulin Antagonists on Protein Kinase C
III. Novel Protein Kinase C Inhibitors
IV. Conclusion
References
Index