Platelets and Their Factors

ISBN-13: 9783642644887 / Angielski / Miękka / 2011 / 753 str.

Franz von Bruchhausen;Ulrich Walter

Opis

Platelets playa fundamental, life-saving role in hemostasis and blood clotting at sites of vascular injury. Unwanted platelet activation and arterial thombus formation are, however, implicated in the onset of myocardial infarction, stroke, and other cardiovascular diseases. Acceptance that platelets play a major role in the pathogenesis of atherosclerosis including coronary heart disease has revolutionized the pharmacological treatment of cardiovascular diseases, and aspirin is now an essential antiplatelet drug and the golden standard for future developments. Yet the search for better and perhaps safer antiplatelet drugs is one of the most active areas of investigation in both basic and clinical research. Platelets, especially human platelets, have also emerged as one of the major models for the study of inter- and intracellular signal transduction pathways. Many biochemists, cell biologists, pharmacologists, pathologists, hematologists, and cardiologists find platelets useful for studying processes such as adhesion, inside-out and outside-in signalling through the plasma membrane, channels, calcium homeostasis, protein kinases, the network of intracellular signal transduction cascades, and the release of vasoactive substances. The aim of the editors has been to compile chapters summarizing the current state-of-the-art information on the biochemistry, cell biology, pharmacology, and physiologic and pathophysiologic roles of human platelets. We hope that this volume represents the major aspects of current platelet research although it is perhaps inevitable that certain areas are covered less thoroughly than others. We would like to acknowledge the excellent help and support of the Springer-Verlag staff, in particular that of Ms. Doris Walker.

Spis treści

Section I: Platelet Development, Morphology and Physiology.- 1 Megakaryocytopoiesis: The Megakaryocyte/Platelet Haemostatic Axis.- A. Introduction.- B. Megakaryocyte Anatomy.- I. Structure.- II. Site of Platelet Production.- III. Ploidy.- C. Megakaryocytopoiesis and Thrombopoiesis.- I. Perturbations of the Steady State.- II. Megakaryocyte Progenitor Cells.- III. Megakaryocyte Growth Factors.- IV. Thrombopoietin/cMpl Ligand.- V. Negative Regulation of Megakaryocytopoiesis.- D. Signal Transduction Events and Mechanisms of Polyploidisation.- I. Involvement of Protein Kinase C in Megakaryocyte Differentiation.- II. Induction of Tyrosine Phosphorylation by TPO.- III. Cell Cycle Control and Polyploidisation.- E. Megakaryocytes in Atherosclerosis.- F. Conclusion.- References.- 2 Human Platelet Morphology/Ultrastructure.- A. General Morphology: Shape and Properties of Platelets.- B. Electron-Microscopic Techniques.- C. Morphometric Data.- D. Ultrastructure of Platelets.- I. Cytosol and Cytoskeleton.- 1. Cytosol.- 2. Submembranous Cytoskeleton.- 3. Contractile Gel.- II. Plasmalemma and Surface.- III. Surface-Connected Membranes.- 1. Surface-Connected (Open Canalicular) System.- 2. Coated Membranes.- IV. Cell Organelles.- 1. Mitochondria.- 2. Dense Tubular System.- 3. Alpha-Granules.- 4. Dense Granules.- 5. Lysosomes and Peroxisomes.- E. Functional Morphology.- I. Focal Adhesion Contacts.- II. Internalization and Endocytosis.- 1. Receptor Transport and Membrane Recycling.- 2. Internalization of Ligands by the Contractile Gel.- III. Exocytosis.- 1. Secretory Pathway.- 2. Shedding of “Microparticles”.- F. Synopsis and Conclusions.- References.- 3 Platelet Adhesion.- A. Introduction.- B. The Vessel Wall.- C. Platelet Adhesion Under Flow Conditions.- D. Platelet Adhesion to the Adhesive Proteins.- I. Von Willebrand Factor.- II. Collagen.- III. Fibronectin.- IV. Fibrin(ogen).- V. Other Proteins.- 1. Laminin.- 2. Thrombospondin.- 3. Proteoglycans.- E. Conclusion.- References.- 4 Platelet Aggregation.- A. Introduction.- B. Mechanism of Platelet Aggregation.- I. The Glycoprotein IIb-IIIa Complex.- II. Adhesive Ligands of the GPIIb-IIIa Complex.- III. Redistribution of the GpIIb-IIIa Complex and Internalization of the Ligands.- C. Platelet Aggregation Testing.- I. Sample Preparation.- II. Optical Aggregometry.- III. Lumi-aggregometry.- IV. Determination of Platelet Aggregation by Particle Counting 90.- V. Potential and Limitations of Platelet Aggregation Testing.- D. Inhibition of Platelet Aggregation as a Therapeutic Principle.- E. Conclusions.- References.- Section II: Platelet Biochemistry, Signal Transduction.- 5 Platelet Receptors: The Thrombin Receptor.- A. Introduction.- B. The Seven-Transmembrane Domain Receptor.- I. Structure and Activation Mechanism.- II. Receptor Desensitization and Resensitization.- C. Glycoprotein Ib.- D. Receptor Signaling and Platelet Responses.- E. Thrombin Receptor Inhibitors.- References.- 6 Platelet ADP/Purinergic Receptors.- A. Introduction.- B. Platelet Responses to ADP.- I. Platelet Functions.- 1. Shape Change.- 2. Binding of Fibrinogen.- 3. ADP-Induced Platelet Aggregation.- 4. Desensitization.- II. Signal Transduction.- 1. Changes in Cytosolic Free Calcium Concentration.- 2. Changes in Inositol Phospholipids.- 3. Inhibition of Adenylyl Cyclase.- 4. Involvement of G Proteins.- C. Platelet ADP Receptors.- I. Binding Studies.- II. ADP-Binding Proteins.- III. The P2 Purinoceptor Family.- IV. Current Hypothesis of a Two-Receptor Model.- V. Future Perspectives.- D. Conclusions.- References.- 7 Platelet Prostaglandin Receptors.- A. Introduction.- B. Thromboxane A2 Receptor.- I. Structure and Ligand Binding Specificity.- II. Signal Transduction.- III. Regulation.- C. Prostacyclin Receptor.- I. Structure and Ligand Binding Specificity.- II. Signal Transduction.- III. Regulation.- D. Prostaglandin D Receptor.- I. Structure.- II. Ligand Binding Specificity and Signal Transduction.- E. Prostaglandin E Receptor Subtype; the EP3 Receptor.- References.- 8 Platelet Adhesion and Aggregation Receptors.- A. Introduction.- B. Platelet Surface Glycoproteins.- C. The Glycoprotein Ib-V-IX Complex.- I. Introduction.- 1. Glycoprotein Ib?.- 2. Glycoprotein Ib?.- 3. Glycoprotein IX.- 4. Glycoprotein V.- 5. Polymorphism Within GPIb?.- II. Function of the Glycoprotein Ib-V-IX Complex.- 1. Bleeding Disorders.- a) Bernard-Soulier Syndrome.- b) Platelet-Type von Willebrand’s Disease.- 2. GPIb-vWf Binding.- 3. Non-physiological Activators of the GPIb/vWF Axis.- III. Expression of GPIb-V-IX.- D. GPIIb-IIIa.- E. GPIa-IIa.- F. GPIc-IIa.- G. GPIc’-IIa.- H. CD36 (GPIIIb or GPIV).- I. P-selectin (CD62, GMP-140, PADGEM).- J. PECAM-1 (CD31).- K. Inhibition of Platelet Adhesion/Aggregation as a Prophylactic Tool or for Treatment of Acute Thrombotic Events.- References.- 9 Platelet G Proteins and Adenylyl and Guanylyl Cyclases.- A. Introduction.- B. G Proteins.- I. General Considerations.- 1. Activation of G Proteins.- 2. Diversity of G Proteins.- 3. Structure of G Proteins.- 4. Co- and Posttranslational Modifications of Platelet G Proteins.- II. G Proteins Expressed in Platelets.- III. G Proteins as Modulators of Platelet Activation.- 1. Platelet-Activating G Proteins.- 2. Platelet-Inhibiting G Proteins.- C. Adenylyl Cyclases.- D. Guanylyl Cyclases.- I. Membrane-Bound Guanylyl Cyclases.- II. Soluble Guanylyl Cyclases.- 1. Regulation of Soluble Guanylyl Cyclases.- 2. Biosynthesis of Nitric Oxide.- III. cGMP Receptor Proteins.- 1. cGMP-Dependent Protein Kinases.- 2. cGMP-Gated Channels.- E. Physiological Role of Cyclic Nucleotides in Platelets.- I. cGMP-Formation in Platelets.- II. cGMP- and cAMP-Dependent Protein Kinases in Platelets.- III. Substrates for cAMP- and cGMP-Dependent Protein Kinases in Platelets.- IV. Cellular Responses Leading to Platelet Inhibition.- References.- 10 Platelet Phosphodiesterases.- A. Introduction.- B. Catalytic and Regulatory Properties of Human Platelet Phosphodiesterases.- I. cGMP-Stimulated Phosphodiesterase.- II. cGMP-Inhibited Phosphodiesterase.- III. cGMP-Specific Phosphodiesterase.- C. Synergistic Inhibition of Platelet Function by Cyclic Nucleotide Elevating Agents.- D. Regulation of Platelet Phosphodiesterases by Insulin.- E. Effect of Phosphodiesterase Inhibitors on Platelet Function.- I. General Aspects.- II. Specificity.- F. Concluding Remarks.- References.- 11 Platelet Phospholipases C and D.- A. Introduction.- B. Receptor-Mediated Activation of Phosphoinositide-Specific Phospholipase C.- I. Activation of Phosphoinositide-Specific Phospholipase C in Platelets.- II. Formation of Second Messengers.- 1. Inositol 1,4,5-trisphosphate.- 2. 1,2-Diacylglycerol.- 3. Phosphatidic Acid and Lysophosphatidic Acid.- III. Modulation of Phosphoinositide-Specific Phospholipase C.- C. Regulation of Phosphoinositide-Specific Phospholipase C.- I. Multiplicity of Phosphoinositide-Specific Phospholipase C.- II. G-Protein-Mediated Phospholipase C-? Activation.- III. Tyrosine Kinase-Mediated Phospholipase C-?Activation.- D. Roles and Regulation of Phospholipase D in Platelet Activation.- I. Activation of Phospholipase D in Platelets.- II. Regulation of Phospholipase D Activity.- E. Remarks.- References.- 12 Protein Kinase C and Its Interactions with Other Serine-Threonine Kinases.- A. Introduction and Definition.- B. Molecular Structure and Heterogeneity.- C. PKC Activation by Lipid Mediators in Platelets.- D. PKC Substrates, Binding Proteins, and Translocation.- E. Functional Roles for PKC in Platelets.- F. Relation of PKC Activation to Other Platelet Serine-Threonine Kinases and Their Effectors.- G. Abnormalities of Platelet PKC in Disease.- H. Summary and Future Areas of Research.- References.- 13 Platelet Protein Tyrosine Kinases.- A. Background.- B. Protein Tyrosine Kinases in Platelets.- I. Src Family Kinases.- 1. Src.- 2. Other Src Family Members.- II. Syk.- III. JAK Family Kinases.- IV. Focal Adhesion Kinase (FAK).- V. Receptor Protein Tyrosine Kinases.- C. Potential Roles of Protein Tyrosine Kinases in Platelet Functions.- I. Second Messenger Pathways.- 1. Phospholipases.- 2. Phosphoinositide 3-Kinase.- 3. GTP-Binding Proteins.- 4. Calcium.- 5. Cyclic Nucleotides.- II. Platelet Responses.- 1. Shape Change.- 2. Aggregation.- 3. Adhesion.- References.- 14 Protein Phosphatases in Platelet Function.- A. Introduction.- B. Protein Serine/Threonine Phosphatases in Platelets.- I. Classification of Serine/Threonine Protein Phosphatases.- II. Inhibitors of Protein Serine/Threonine Phosphatases.- III. The Presence of Protein Serine/Threonine Phosphatases in Platelets.- IV. Effect of Okadaic Acid and Calyculin A in Platelets.- V. Dephosphorylation of Cofilin in Platelets.- VI. Protein Serine/Threonine Phosphatases in Platelets: Concluding Remarks.- C. Protein Tyrosine Phosphatases.- I. Classification of Protein Tyrosine Phosphatases.- II. Distribution of Protein Tyrosine Phosphatases in Platelets.- III. Regulation of Tyrosine Phosphorylation by Irreversible Platelet Aggregation.- IV. Effect of Vanadate and Its Derivatives in Platelets.- V. Effect of Phenylarsine Oxide in Platelets.- VI. Possible Role of Protein Tyrosine Phosphatases in Ca2+ Entry.- VII. Regulation of Protein Tyrosine Phosphatases by Serine/Threonine Phosphorylation.- VIII. Protein Tyrosine Phosphatases in Platelets: Concluding Remarks.- D. Dual Specificity Protein Phosphatases.- E. Concluding Remarks.- References.- 15 Ca2+ Homeostasis in Human Platelets.- A. Introduction.- I. Ca2+ Homeostasis.- B. Maintenance of Low Cytosolic Ca2+ Concentrations.- I. Platelet SERCAs.- II. Membrane Organisation, Properties and Regulation of Platelet SERCAs.- III. Organellar Distribution of Platelet SERCA Pumps.- IV. Plasma Membrane Calcium ATPases.- V. Platelet PMCAs.- VI. Na+/Ca2+ Exchanger.- C. Mechanisms of Ca2+ Elevation in Platelets.- I. Ca2+ Release from Intracellular Stores.- 1. Inositol (1,4,5) Trisphosphate.- 2. General Properties of IP3Rs.- 3. Platelet IP3Rs.- 4. In(1,4,5)P3-Induced Ca2+ Release from Platelet Intracellular Stores.- II. Nature of Ca2+ Release from Intracellular Stores.- III. Ca2+ Oscillations in Platelets.- IV. Ca2+ Influx Mechanisms.- V. Capacitative or Store-Regulated Ca2+ Entry.- VI. Possible Direct Involvement of Second Messengers in Ca2+ Entry.- VII. Integrin-Associated Plasma Membrane Ca2+ Flux.- VIII. Ca2+ Influx Via Receptor-Operated Ca2+ Channel (ROC).- IX. Cyclic Nucleotide Effects on Ca2+ Influx.- References.- 16 Regulation of Platelet Function by Nitric Oxide and Other Nitrogen- and Oxygen-Derived Reactive Species.- A. Introduction.- B. A Historical Perspective.- C. Nitric Oxide Synthase Isoenzymes.- I. General Characteristics.- II. Platelet Nitric Oxide Synthase.- III. The Endothelial NOS.- IV. Nitric Oxide Synthase Reaction.- V. Metabolic Fate of NO.- VI. Interactions of NO with Biomolecules.- VII. Nitric Oxide — Physiological Regulator of Platelet Function.- VIII. Role of NO in the Pathogenesis of Vascular Disorders.- IX. Pharmacological Regulation of Platelet Function by NO Gas and NO Donor Drugs.- D. Other Oxygen- and Nitrogen-Derived Reactive Species.- I. Mechanisms of Action of Oxygen-Derived Radicals on Platelets.- 1. Thromboxane Generation.- 2. Cyclic Nucleotides.- 3. Stimulation of Platelet Serotonin Transport.- 4. Activation of Platelet Receptors.- 5. Formation of Nitric Oxide Donors.- E. Conclusions.- References.- 17 Platelet 5-Hydroxytryptamine Transporters.- A. Introduction.- B. The Plasma Membrane 5-Hydroxytryptamine Transporter (SERT).- I. Ionic Requirements.- 1. Coupling to Na+.- 2. Coupling to Cl-.- 3. Coupling to K+.- II. Reversal of Transport.- III. Mechanism.- IV. Purification.- V. Cloning.- VI. Regulation.- C. Dense Granule Membrane Vesicles.- I. Driving Forces.- II. Purification.- III. Cloning.- References.- Section III: Platelet-Derived Factors.- 18 Dense Granule Factors.- A. Introduction.- B. Contents of Platelets.- I. Nucleotides.- II. Divalent Cations.- III. Amines.- IV. Other.- C. Storage Mechanisms.- D. Species Differences.- E. Membrane Proteins.- F. Discussion and Comments.- References.- 19 Protein Granule Factors.- A. Introduction.- B. Platelet Proteins.- C. Platelet-Derived Growth Factors.- D. Thrombospondin.- E. Proteins Similar or Identical to Plasma Proteins.- F. Enzymes.- G. Summary and Conclusions.- References.- 20 Lysosomal Storage.- A. Introduction..- I. Lysosomes in General.- II. Platelet Lysosomes.- B. Lysosomal Hydrolases in Platelets.- I. Glycosidases.- 1. Secretion.- 2. Subcellular Localization.- II. Proteinases.- III. Phospholipases.- IV. Other.- C. Lysosomal Membrane Proteins.- D. Discussion and Comments.- References.- 21 Thromboxane A2 and Other Eicosanoids.- A. Introduction.- B. Platelet Arachidonic Acid Metabolism.- I. Metabolites.- II. Sources of Arachidonic Acid.- III. Release of Arachidonic Acid.- 1. Phospholipase A2.- 2. Other Routes of Arachidonic Acid Liberation.- C. Eicosanoids Affecting Platelet Function.- I. Thromboxane A2.- 1. Introduction.- a) Thromboxane A2 Receptors.- b) Signal Transduction.- ?) Intracellular Calcium.- ?) Alkalinization of Intraplatelet pH.- ?) Protein Kinase C Activation.- ?) Tyrosine Phosphorylation.- ?) Myosin Light Chain Kinase.- II. Prostacyclin (PGI2, Epoprostanol).- III. 8-Epi-prostaglandin F2?.- IV. Prostaglandin D2 (PGD2).- V. 12-Hete (12-Hydroxyeicosatetraenoic Acid).- D. Alterations in Thromboxane A2 Synthesis in Disease States.- I. Diabetes Mellitus.- II. Acute Coronary Artery Syndromes.- III. Pregnancy-Induced Hypertension.- IV. Cerebral Ischemia.- V. Homocystinuria.- VI. Sickle Cell Disease.- VII. Effects of Fish Oils.- E. Alterations in Thromboxane A2 Receptors in Disease States.- I. Acute Coronary Artery Syndromes.- II. Pregnancy-Induced Hypertension.- III. Diabetes Mellitus.- IV. Regulation by Androgenic Steroids.- F. Aspirin, Thromboxane Synthase Inhibitors, and Thromboxane A2 Receptor Antagonists in Coronary Artery Disease.- References.- 22 Platelet-Activating Factor: Biosynthesis, Biodegradation, Actions.- A. Introduction.- B. Biosynthesis of PAF in Mammalian Cells.- C. Catabolism of PAF in Mammalian Cells.- D. PAF and Bacteria.- E. PAF and Yeast Cells, Protozoans, Amoebas, and Parasites.- F. Effects of PAF on Cell Proliferation.- G. Some Effects of PAF on Several Cell Functions and Tissue Structures.- H. Conclusion.- References.- 23 Qualitative and Quantitative Assessment of Platelet Activating Factors.- A. PAF Molecular Diversity.- B. Estimation of PAF Activity by Bioassay.- I. Platelet Bioassay.- 1. Rabbit Platelet Bioassay.- 2. Platelet Desensitization.- 3. PAF Carriers in Platelet Bioassay.- 4. PAF Molecular Diversity in Platelet Bioassay.- II. Other.- C. Estimation of PAF Activity by Radioimmunoassay (RIA).- I. RIA Development and Use.- II. PAF Molecular Diversity in RIA.- D. Estimation of PAF by Radioreceptor Assay.- E. Estimation of PAF Based on [3H]Acetate Incorporation.- F. Analysis of PAF by Mass Spectrometry.- I. Analysis of Intact PAF.- II. Analysis of PAF After Derivatization.- G. Concluding Comments.- References.- 24 Biosynthetic Inhibitors and Receptor Antagonists to Platelet Activating Factor.- A. PAF: Historical Perspective and Pathology.- B. Biosynthesis Inhibitors.- I. Phospholipase PLA2 Inhibitors.- II. Lyso-PAF-Transferase Inhibitors.- C. Preclinical and Clinical PAF Receptor Antagonists.- I. Abbott Laboratories.- II. Alter S.A.- III. Boehringer Ingelheim KG.- IV. British Biotechnology Ltd.- V. Eisai Co., Ltd.- VI. Fujisawa Pharmaceutical Co.- VII. Hoffmann-La Roche and Co., Ltd..- VIII. Leo Pharmaceutical Products Ltd..- IX. Merck Sharp and Dohme Research Laboratories.- X. Ono Pharmaceutical Co., Ltd..- XI. Pfizer Laboratories.- XII. Rhône-Poulenc Santé Laboratories.- XIII. Sandoz Research Institute.- XIV. Sanofi Research.- XV. Schering-Plough Research Institute.- XVI. Solvay Pharma Laboratories.- XVII. Sumitomo Pharmaceuticals Co., Ltd..- XVIII. Takeda Chemical Co., Ltd..- XIX. Uriach S.A..- XX. Yamanouchi Pharmaceutical Company.- XXI. Yoshitomi Pharmaceutical Industries Ltd..- D. Conclusions.- References.- Section IV: Clinical Aspects of Platelets and Their Factors.- 25 Platelets and the Vascular System: Atherosclerosis, Thrombosis, Myocardial Infarction.- A. Introduction.- B. Atherosclerosis.- C. Thrombosis.- D. Myocardial Infarction.- E. Methodology of Radiolabeling of Platelets.- F. Studies with Radiolabeled Platelets.- I. Platelet Kinetics.- II. Imaging.- 1. Atherosclerosis.- 2. Thrombosis.- 3. Myocardial Infarction.- G. Platelet Aggregation.- H. Conclusions.- References.- 26 Platelets, Vessel Wall, and the Coagulation System.- A. Platelet-Endothelium Interaction.- I. Role of Platelets in Maintaining Vascular Integrity.- II. Control of Platelet Reactivity by Endothelial Cells.- 1. 13-Hydroxy-octadecadienoic Acid (13-HODE) — An Antiadhesive Fatty Acid Metabolite.- 2. Endothelium-Derived Platelet Inhibitors.- 3. Platelet Effects on PGI2 and EDRF/NO Synthesis.- 4. Mechanisms of Platelet Inhibition by PGI2 and EDRF/NO.- 5. Endothelial-Bound Antiplatelet Factors.- 6. Platelet Adhesion to Endothelial Cells.- III. Platelet-Mediated Inflammatory and Procoagulant Alterations of Endothelial Cells.- B. Platelets and Coagulation.- I. Membrane-Dependent Reactions in Blood Coagulation.- II. Platelet Procoagulant Activity.- III. Mechanisms Involved in the Maintenance of Membrane Lipid Asymmetry.- IV. Mechanisms Involved in the Expression of Procoagulant Activity.- V. Platelet Microvesicles.- VI. Platelets and Coagulation Disorders.- 1. Scott Syndrome.- 2. Antiphospholipid Syndrome.- 3. Factor V Quebec.- VII. Anticoagulant Activities of Platelets and Microvesicles.- VIII. Role of Platelets in Fibrinolysis.- References.- 27 Platelet Flow Cytometry — Adhesive Proteins.- A. Introduction.- I. Procedures for the Diagnosis of Platelet Disease States.- 1. Problems.- 2. Requirements.- B. Single Platelet Flow Cytometry (SPFC).- I. Principle.- II. Pitfalls and Standardization Requirements.- III. Assay Systems.- C. Platelet Adhesion Molecules as Diagnostic Targets.- I. Megakaryocytic Conditioning.- II. Platelet Membrane Processing.- III. Defining Diagnostic Epitopes.- 1. The Constitutive Stain.- 2. The Functional Stain.- IV. Platelet-Leukocyte Coaggregates.- D. Applications in Platelet Pathology.- I. Hemorrhagic Diathesis.- II. Thrombotic Diathesis.- III. Inflammation.- E. Pharmacology.- References.- 28 Pathological Aspects of Platelet-Activating Factor (PAF).- A. Introduction.- B. Involvement of PAF in Inflammatory and Allergic Responses.- I. Inflammatory Cellular Responses by PAF.- II. Involvement of PAF in Allergic Reactions.- C. Involvement of PAF in Cardiovascular Diseases.- I. PAF in Vascular Disturbances.- II. PAF in Endotoxin-Induced Shock.- III. Thrombovascular Diseases.- IV. Myocardial Infarction and Stroke.- D. Involvement of PAF in Cerebral Disturbances.- E. PAF in Respiratory Diseases.- I. Bronchial Hyperresponsiveness.- II. PAF in Asthma Bronchiale.- III. Pulmonary Edema.- IV. Adult Respiratory Distress Syndrome (ARDS).- V. Lung Fibrosis.- F. Involvement of PAF in Gastrointestinal Diseases.- I. Gastric Diseases.- II. Intestinal Diseases.- G. Involvement of PAF in Function and Disturbances of Reproduction.- I. Ovulation.- II. Gametocytes (Oocytes, Sperm).- III. Fertilization.- IV. Oviduct Passage and Preimplantation State.- V. Nidation.- VI. Embryonic Development.- H. Involvement of PAF in Skin Diseases.- I. Involvement of PAF in Diseases of Other Organs.- I. Renal Diseases.- II. Hepatic Disturbances.- III. Acute Pancreatitis.- IV. Transplant Rejection.- V. Tumor Growth.- J. Conclusion.- References.- 29 Therapeutic Aspects of Platelet Pharmacology.- Aspirin.- Selective Thromboxane Blockade.- Ticlopidine and Clopidogrel.- Fibrinogen Receptor Antagonism.- References.