Calmodulin Antagonists and Cellular Physiology

Calmodulin Antagonists and Cellular Physiology

1st Edition - January 28, 1985

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  • Editor: Hiroyoshi Hidaka
  • eBook ISBN: 9780323145732

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Description

Calmodulin Antagonists and Cellular Physiology focuses on the biochemistry of calmodulin antagonists as regulators of cellular physiology. Emphasis is placed on the use of calmodulin antagonists as an indicator of calmodulin function. The mechanism of action of calmodulin antagonists and their interactions with calmodulin are explored. This book is comprised of 33 chapters and begins with an introduction to the biochemical aspects of calmodulin as well as its distribution and functions, followed by a discussion on how calmodulin antagonists and other agents modulate Ca2+-dependent regulatory systems. The next section is devoted to the mechanism of action of calmodulin antagonists and includes chapters that examine the interaction of various drugs with calmodulin and the structure-activity relationships of calmodulin antagonists. The effects of calmodulin antagonists on cell proliferation and growth are then discussed. The remaining chapters deal with the role of calmodulin antagonists in cell function and the contractile process, along with their effect on protein kinase C. This monograph will be a useful resource for biochemists as well as students and researchers in biochemistry.

Table of Contents


  • 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

Product details

  • No. of pages: 568
  • Language: English
  • Copyright: © Academic Press 1985
  • Published: January 28, 1985
  • Imprint: Academic Press
  • eBook ISBN: 9780323145732

About the Editor

Hiroyoshi Hidaka

Affiliations and Expertise

Nagoya University School of Medicine

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