The Platelets: Physiology And Pharmacology

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 a-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.

Table of Contents:
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 a-Granule Proteins: Biochemical and Pathological Aspects I. Introduction II. Platelet Factor 4 III. ß-Thromboglobulin-Like Proteins IV. Platelet-Derived Growth Factor V. Thrombospondin VI. Gray Platelet Syndrome: A Deficiency in Platelet a 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 a Adrenoceptor V. The Platelet ß 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