The Platelets

The Platelets: Physiology and Pharmacology is a critical review of the basic platelet systems, methodologic critiques, and platelet involvement in major disease states. This book is composed of 20 chapters that specifically deal with the physiology and biochemistry of the platelet system, along with possibilities for, and consequences of, pharmacologic manipulation. The opening chapters examine the basic processes of platelet aggregation and adhesion. These topics are followed by discussions on the types and functions of platelet α-granule proteins; the aspects of adenine nucleotide levels, regulation, and storage; and receptors for catecholamines and consequences of their agonism. Other chapters are devoted to the metabolism of arachidonic acid, its manipulation, consequences, and metabolite receptors. The discussion then shifts to the second-messenger entities, specifically calmodulin, calcium, and cyclic adenosine monophosphate. A chapter presents the comparisons of man and commonly used laboratory animals concerning platelet behavior variability. Another chapter looks into the use and appropriateness of the use of platelets as models of neurons, with a special emphasis on serotonergic neurons. The remaining chapters contain critical reviews of platelet involvement in diabetes, hypertension and peripheral vascular disease, atherogenesis/atherosclerosis, and ischemic heart disease. These chapters also include specific techniques for platelet analysis, including lumiaggregometry, eicosanoid measurements, and serotonin uptake and release. This book is an invaluable source for pharmacologists, biochemists, researchers, and clinicians who are interested in platelet involvement in disease.

Contributors

Preface

1. Platelet Aggregation

I. Introduction

II. Early Events in Platelet Aggregation

III. Methods of Measurement

IV. Pathways of Platelet Activation

V. Synergisms

References

2. Platelet Adhesion: Past and Present

I. Introduction

II. Platelet Aggregometry versus Mural Thrombogenesis

III. Devices with Undefined Hemodynamics

IV. Hemodynamic Consideration

V. Platelet Accumulation on Surfaces

VI. Effects of Medium Composition

VII. Discrete Monitoring of Platelet Deposition

VIII. Continuous Monitoring of Platelet Deposition

IX. A Paradigm of Mural Thrombogenesis

X. Summary

References

3. Platelet α-Granule Proteins: Biochemical and Pathological Aspects

I. Introduction

II. Platelet Factor 4

III. β-Thromboglobulin-Like Proteins

IV. Platelet-Derived Growth Factor

V. Thrombospondin

VI. Gray Platelet Syndrome: A Deficiency in Platelet α Granules

VII. Platelet-Secreted Proteins as Markers of Platelet Activation in Disease

References

4. Adenine Nucleotides in Blood Platelets

I. Introduction

II. Nucleotide Content of Platelets

III. Compartmentalization of Adenine Nucleotides in Platelets

IV. Determination of Platelet Adenine Nucleotides

V. Platelet Adenine Nucleotide Metabolism

VI. Utilization of Metabolic ATP

VII. Storage Granule Adenine Nucleotides

VIII. Interaction of Released ADP with Platelets

References

5. Platelet Adrenoceptors

I. Introduction

II. General Properties of Adrenoceptors

III. Responses of Platelets to Adrenaline

IV. The Platelet α Adrenoceptor

V. The Platelet β Adrenoceptor

VI. Relationship between Platelet Adrenoceptor Density and the Nature of the Response to Adrenaline in Platelets from Different Mammalian Species

VII. Conclusions

References

6. Platelet Arachidonic Acid Metabolism

I. Introduction

II. Nomenclature

III. Eicosanoid Formation by Platelets: Historical Aspects

IV. Involved Enzymes

V. Effects of Platelet Eicosanoid

VI. Summary

References

7. Hydroperoxide Metabolism and Oxidant Generation in Platelets

I. Arachidonic Acid Metabolism in Platelets

II. Free Radical Generation during Arachidonate Oxygenation

III. Fatty Acid Hydroperoxide Metabolism by Detoxifying Enzymes

IV. Consequences of Escape of Fatty Acid Hydroperoxides

V. Do Oxidants Escape Platelets?

VI. Summary

References

8. Platelet Eicosanoid Receptors

I. Introduction

II. Stimulatory Eicosanoids

III. Inhibitory Eicosanoids

IV. Clinical Considerations

V. Conclusions

References

9. Calmodulin and Platelet Function

I. Introduction

II. Platelet Calmodulin—Identification, Localization, and Purification

III. The Role of Calcium in Platelet Activation

IV. The Effect of Calmodulin Antagonists on Platelet Function

V. Calmodulin-Dependent Enzymes

VI. Conclusion

References

10. Calcium and Cyclic AMP: Antagonistic Modulators of Platelet Function

I. Introduction

II. Relationships between Ca2+, Diacylglycerol, and Protein Kinases

III. Proposed Mechanisms for Mobilization of Calcium

IV. The Relationship between [Ca2+]i and Platelet Responses

V. Mobilization of Calcium and Its Regulation

VI. Regulation of [Ca2+]i by Cyclic AMP

VII. Effects of Ca2+ and Cyclic AMP on Cytoskeleton and Lipid Metabolism

References

11. Regulation of Platelet Cyclic AMP Formation

I. Introduction

II. Hormonal Stimulation of Platelet Adenylate Cyclase

III. Stimulation of Platelet Adenylate Cyclase by Nonhormonal Agents

IV. Hormonal Inhibition of Platelet Adenylate Cyclase

V. Inhibition of Platelet Adenylate Cyclase by Nonhormonal Agents

VI. Conclusions

References

12. Species Variation in Platelet Aggregation

I. Introduction

II. Arachidonic Acid Content in Platelet Lipids and the Profile of Its Metabolites Synthesized by Platelets

III. Adenosine Diphosphate-Induced Platelet Aggregation and Effects of Inhibitors of Arachidonic Acid Metabolism

IV. Inhibition of ADP-Induced Platelet Aggregation by Prostaglandins

V. Inhibition of ADP-Induced Platelet Aggregation by Structural Analogs of ADP

VI. Collagen-Induced Aggregation and the Role of Inhibitors of Arachidonic Acid Metabolism

VII. Epinephrine-Induced Platelet Aggregation

VIII. Summary

References

13. Platelets as Pharmacologic Models for the Receptors and Biochemistry of Monoaminergic Neurons

I. Introduction: Peripheral Models for Central Nervous System Neurotransmitters

II. Platelets as Pharmacologic Models of Serotonergic Neurons

III. Platelets as Pharmacologic Models of Adrenergic Neurons

References

14. Platelet Involvement in Diabetes Mellitus

I. Introduction

II. Platelet Function in Diabetes Mellitus

III. Endothelial Function in Diabetes Mellitus

IV. Collaborative Trials of Antiplatelet Agents in Diabetic Vascular Disease

V. Summary and Conclusions

References

15. Platelets in Hypertension and Peripheral Vascular Disease

I. Introduction

II. Platelets in Hypertension

III. Platelets in Peripheral Vascular Disease

References

16. The Role of Platelets in Atherogenesis/Atherosclerosis

I. Introduction

II. Thrombosis as an Initiating Event

III. Experimental Atherogenesis—The Response to Injury

IV. The Importance of the Platelet in Atherogenesis

V. Control of Intimal Hyperplasia

VI. Pituitary Involvement in Intimal Hyperplasia

VII. Arterial Occlusion

VIII. Therapy

IX. Conclusion

References

17. Platelets and Ischemic Heart Disease

I. Introduction

II. Primary Cardiac Arrest

III. Angina Pectoris

IV. Acute Myocardial Infarction

V. The Antiplatelet Strategies in Prevention of Coronary Heart Disease

References

18. The Lumi-Aggregometer as a Research and Clinical Tool

I. Introduction

II. Basic Principles and Experimental Details of the Use of the Lumi-Aggregometer

III. Platelet Response to Stimuli

IV. Analysis of Platelet Stimulation

V. Response of Platelets to Different Agonists

VI. Patterns of Aggregation and Secretion

VII. Research Problems in Stimulus-Response Coupling Using the Lumi-Aggregometer

VIII. Use of the Lumi-Aggregometer in Clinical Research

References

19. Measurement of Platelet Eicosanoid Compounds

I. Introduction

II. Methodology

III. Metabolic Aspects of Platelet Eicosanoid Measurements

IV. Recent Developments in Platelet Polyunsaturated Fatty Acid Metabolism

References

20. Characteristics of Serotonin Uptake and Release by Platelets

I. Introduction

II. Platelet Serotonin Uptake

III. Release of 5-HT by Platelets

IV. Concluding Remarks

References

Index