Introduction: Historical Aspects of Alkyl Lipids and Their BiologicallyActive Forms (Ether Lipids,Platelet-Activating Factor, andAntihypertensive Renal Lipids).- I. Methodology and Chemistry.- 1. Chemical Synthesis and Mass Spectrometry of PAF.- 1. Introduction.- 2. Chemical Synthesis of PAF.- 3. Mass Spectrometry.- References.- 2. Chromatographic Analyses of Ether-Linked LipidsInvolved in PAF Metabolism.- 1. Introduction.- 2. Chromatographic Separations of PAF and Related Analogs.- 3. Analyses of PAF-Related Lipids.- 4. Summary.- References.- II. Composition.- 3. Composition of Alkyl Ether-Linked Phospholipids in Mammalian Tissues.- 1. Introduction.- 2. Contents of Alk-1-enylacyl, Alkylacy1, and Diacyl Phospholipids in Mammalian Tissues.- 3. Fatty Chain Composition and Molecular Species of ther and Diacyl Phospholipids.- 4. Structure of Naturally Occurring PAF.- References.- III. Enzymes.- 4. Enzymatic Pathways for Platelet-Activating Factor, Related Alkyl Glycerolipids, their Precursors.- 1. Introduction.- 2. Precursors of Ether Lipids: Fatty Alcohols and Acyldihydroxyacetone-P.- 3. Formation of the Alkyl-Ether Bond in Lipids: Alkyldihydroxyacetone-P, the First Detectable Intermediate.- 4. Biosynthesis of l-Alkyl-2-lyso-sn-glycero-3-P, a Branchpoint in PAF Metabolism: Alkyldihydroxyacetone-P, Alkyldihydroxyacetone, or Alkylglycerols as Precursors.- 5. Biosynthesis of Alkylacetylglycerols, a Direct Precursor of PAF.- 6. Biosynthesis of PAF via the DTT-Insensitive Cholinephosphotransferase.- 7. Biosynthesis of Alkylacylglycerols.- 8. Conversion of Alkylacylglycerols to Alkylacylglycerophosphocholines, the Stored Precursor of PAF.- 9. Activation of PAF via the PAF Cycle: Role of Phospholipase A2 and Acetyltransferase with Lyso-PAF as the Intermediate.- 10. Inactivation of PAF via the PAF Cycle: Role of Acetylhydrolase and the Subsequent Conversion of Lyso-PAF to Alkylarachidonoylglycerophosphocholines via a Transacylase.- 11. Cleavage of the Alkyl-Ether Bond: Pte°H4-Dependent Alkylmonoxygenase.- 12. Lysophospholipase D.- 13. Phospholipase C.- 14. Summary.- References.- 5. Enzymatic Control of the Cellular Levels of Platelet-Activating Factor.- 1. Cell Types and Stimuli in the Production of PAF.- 2. Pool Sizes of PAF Precursors.- 3. Alkyllyso-GPC: Acetyl-CoA Acetyltransferase.- 4. Dithiothreitol-Insensitive Cholinephosphotransferase.- 5. Alkylacetyl-GPC Acetylhydrolase.- 6. Phospholipase A2.- 7. Conclusions.- References.- IV. Antagonists, Agonists, and Receptors.- 6. Platelet-Activating Factor Binding to Specific Cell Membrane Receptors.- 1. Introduction.- 2. Methods for Quantifying PAF Binding.- 3. PAF Binding to Intact Cells.- 4. Characteristics of PAF Binding to Platelets.- 5. PAF Binding to Membrane Preparations.- 6. Isolation of the PAF Receptor.- 7. PAF Receptor Antagonists.- 8. Mechanisms of Activating Signal Transduction.- 9. Specific Desensitization to PAF.- References.- 7. The Chemical and Biological Properties of PAF Agonists, Antagonists and Biosynthetic Inhibitors.- 1. Introduction.- 2. PAF Agonists.- 3. PAF Antagonists.- 4. Inhibitors of PAF Biosynthesis.- 5. Conclusions.- References.- 8. Conformational Properties of the PAF-Acether Receptor on Platelets Based on Structure—Activity Studies.- 1. Introduction.- 2. Presence and Characteristics of PAF-Acether Receptors.- 3. Structure-Activity Relations for PAF-Acether Agonists.- 4. Antagonists of PAF-Acether.- 5. Conformation of Specific Membrane PAF-Acether Binding Sites and Its Modification During Cell Activation.- References.- V. Biochemical and Biological Aspects in Specific Cells and Tissues.- 9. Diversity of the Biochemical and Biological Behavior of Platelet-Activating Factor.- 1. Introduction.- 2. Metabolic Alterations Initiated by Platelet-Activating Factor in Various Tissues and Organs.- 3. Summary.- References.- 10. Extracellular and Intracellular Activities of PAF.- 1. Introduction.- 2. Requirement for Cell Stimulation to Initiate PAF Synthesis.- 3. PAF as a Mediator.- 4. Harmful and Beneficial Aspects of Extracellular PAF Action: A Dualistic Problem.- 5. Intracellular PAF.- 6. Summary.- References.- 11. Interrelationships in the Metabolism of Platelet-Activating Factorand Arachidonate in Neutrophils.- 1. Metabolic Pathways of PAF in Neutrophils.- 2. Associations in the Metabolism of Archidonate and PAF in Neutrophils.- 3. Related Interactions of PAF and Arachidonate.- 4. Conclusions.- References.- 12. Platelet-Activating Factor: Mechanisms of Cellular Activation.- 1. Introduction.- 2. Actions of PAF and Structural Analogs.- 3. PAF Receptors.- 4. PAF Antagonists.- 5. PAF and GTP Proteins.- 6. PAF and Ca2+.- 7. PAF and Other Lipid Mediator Systems.- 8. Conclusions.- References.- 13. The Role of Platelet-Activating Factor in Inflammation.- 1. Introduction.- 2. Release of PAF in in Vitro Models of Hypersensitivity Reactions.- 3. Resease of PAF in Vivo in Various Types of Hypersensitivity Reactions.- 4. Tissue Injury Induced by Systemic or Local Administration of PAF in Laboratory Animals.- 5. Release of PAF Induced by Nonimmunological Stimuli.- 6. Conclusions.- References.- 14. The Production of Platelet-Activating Factor by Cultured Human Endothelial Cells: Regulation and Function.- 1. Introduction.- 2. Cultured Endothelial Cells Derived from Umbilical Vein Produce PAF.- 3. Regulation of PAF Production in Endothelial Cells.- 4. Interaction of PAF and Eicosanoid Metabolism in Endothelial Cells.- 5. Function of Endothelial-Associated PAF.- 6. Conclusions.- References.- 15. Bronchopulmonary Pharmacology of PAF-Acether.- 1. Introduction.- 2. Effects of PAF-Acether on the Bronchorespiratory System.- 3. Physiopathology of PAF-Acether with Respect to Pulmonary Functions.- References.- 16. Platelet-Activating Factor: A Secretory Product from Phagocytes.- 1. Introduction.- 2. In Vivo Studies.- 3. Pathophysiological Consequences of the Generation of PAF-Acether.- 4. Modulation of PAF-Acether Generation in PolymorphonuclearLeukocytes.- 5. Modulation of the Biosynthesis of PAF-Acether in Splenic Microsomes.- 6. Concluding Remarks.- References.- 17. Functions of PAF in Reproduction and Development: Involvement of PAF in Fetal Lung Maturation and Parturition.- 1. Introduction.- 2. Identification and Distribution of PAF in Human Amniotic Fluid.- 3. PAF Biosynthesis and Function During Fetal Lung Maturation.- 4. Role of PAF in the Initiation of Parturition.- References.- 18. Effect of PAF on the Cardiovascular System.- 1. Introduction.- 2. Systemic Effects of PAF.- 3. PAF-Induced Shock.- 4. Effect of PAF on Blood Vessels and the Microcirculation.- 5. Antihypertensive Polar Renomedullary Lipids (APRL).- 6. Cardiac and Coronary Effects of PAF.- 7. Summary.- References.- 19. Biosynthesis and Release of PAF-Acether by Mouse Bone Marrow-Derived Mast Cells.- 1. Introduction.- 2. Generation of PAF-Acether from Mast Cells.- 3. Biosynthesis of PAF-Acether by Mouse Bone Marrow-Derived Mast Cells.- 4. Concluding Remarks.- References.- VI. Antitumor Analogs of PAF.- 20. Antineoplastic Actions of Ether Lipids Related to Platelet-Activating Factor.- 1. Introduction..- 2. Activity of Alkyl-Lysophospholipid Derivatives and Other Ether Lipid Derivatives on Experimental Tumor Growth in Vivo.- 3. Activity of Alkyl-Lysophospholipid Derivatives and Other Ether Lipids on Experimental Metastasis in Vivo.- 4. Influence of Alkyl-Lysophospholipid Derivatives on Tumorigenesis.- 5. Mode of Action: Experimental Evidence and Hypothesis.- 6. Preclinical Screening of Various Ether Lipids and Derivatives for Antineoplastic Activity.- 7. Clinical Pilot Studies with ET-18-OCH3 as an Alkyl-Lysophospholipid of the First Generation.- 8. Conclusions and Future Aspects.- References.