Calmodulin Antagonists and Cellular Physiology - 1st Edition - ISBN: 9780123472304, 9780323145732

Calmodulin Antagonists and Cellular Physiology

1st Edition

Editors: Hiroyoshi Hidaka
eBook ISBN: 9780323145732
Imprint: Academic Press
Published Date: 28th January 1985
Page Count: 568
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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



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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


22. Contraction in Vas Deferens and Myometrium during Prolonged Exposure to Calcium-Free Solution

I. Introduction

II. Methods

III. Results

IV. Discussion


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


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


25. Elucidation of Regulatory Mechanism of Tyrosine Hydroxylase and Tryptophan Hydroxylase by Calmodulin Antagonists

I. Introduction

II. Tyrosine Hydroxylase

III. Tryptophan Hydroxylase

IV. Conclusion


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


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


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


29. A Calmodulin and Calcium-Related Physiological Disorder (Bitter Pit) of Apples

I. Introduction

II. Materials and Methods

III. Results and Discussion

IV. Conclusion


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


31. Immobilized Drugs in Protein and Peptide Isolation

I. Background

II. Antagonists Immobilized on Agarose

III. Antagonists Immobilized on Silica

IV. Summary


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


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




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© Academic Press 1985
Academic Press
eBook ISBN:

About the Editor

Hiroyoshi Hidaka

Affiliations and Expertise

Nagoya University School of Medicine

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