The Prostaglandins

1 Aspirin and Prostaglandins.- I. Introduction.- II. Inhibition of Prostaglandin Synthetase from Different Species and Tissues by Nonsteroid Anti-Inflammatory Agents.- A. Absolute Potencies.- B. Relative Potencies.- III. Relationship between Potency of Aspirin-Like Drugs Against Prostaglandin Synthetases In Vitro and Anti-Inflammatory Activity.- A. Variations in Potency.- B. Drug Concentrations in Plasma.- IV. Contribution of Prostaglandins to the Inflammatory Process.- A. Prostaglandin Release.- B. Release of Chemical Mediators.- C. Possible Control Mechanisms for Prostaglandin Biosynthesis and Release.- D. Inflammatory Effects of Prostaglandins.- V. Relationship between In Vivo Inhibition of Prostaglandin Generation and Therapeutic Effects of Nonsteroid Anti-Inflammatory Drugs.- VI. Side-Effects of Nonsteroid Anti-Inflammatory Agents.- VII. Use of Nonsteroid Anti-Inflammatory Drugs as a Test for the Involvement of Prostaglandins in Some Biological Systems.- A. Intestinal Smooth Muscle Tone.- B. Contractions of the Uterus.- C. Contribution of Prostaglandins to Ovary Function.- D. Control of Lipolysis.- E. Control of Release of the Sympathetic Mediator.- F. Local Regulation of Blood Flow.- VIII. Conclusions.- IX. References.- 2 The Thyroid Gland.- I. Introduction.- II. Occurrence and Synthesis of Prostaglandins in the Thyroid.- A. Normal Thyroid.- B. Medullary Carcinoma of the Thyroid.- C. Prostaglandin Synthesis in the Thyroid.- III. Effects of Prostaglandins on Thyroid Gland Metabolism.- A. The Adenylate Cyclase-Cyclic AMP System.- B. Iodine Metabolism and Thyroid Hormone Secretion.- C. Glucose Oxidation.- D. 32P Incorporation into Phospholipid.- E. Conclusions.- IV. Interrelationships of Prostaglandins and TSH.- A. Prostaglandin Analogues.- B. Combined Actions of Prostaglandins and TSH.- C. Dissociation of TSH and Prostaglandin Effects.- D. Conclusions.- V. Summary.- VI. References.- 3 The Mature Erythrocyte.- I. Introduction.- II. Prostaglandins in the Erythrocyte.- A. Synthesis and Release.- B. Metabolism and Inactivation.- C. Binding.- D. Uptake and Distribution.- III. Action on the Mechanical Properties of the Red Cell.- A. Deformability.- B. Hemolysis.- IV. Effects on Obligatory Cation Exchange.- A. Monovalent Cations.- B. Divalent Cations.- V. Metabolic Effects of Prostaglandins.- A. ATP and A TP-Regulating Enzymes.- B. Cyclic AMP.- VI. Effects on Hemoglobin.- VII. Implications in the Pathological State.- VIII. Prostaglandin Antagonists.- IX. Use of Prostaglandins in Preparation and Storage of Plasma Concentrates.- XI. Conclusions.- XI. References.- 4 Prostaglandin Dehydrogenase.- I. Introduction.- II. Metabolic Deactivation.- III. PGDH Distribution.- IV. Enzyme Purification.- A. Requirements.- B. Methods.- C. Assays for PGDH Activity.- V. Some Properties of the Purified PGDH.- A. Purity.- B. Stability.- C. Molecular Weight.- D. pH.- E. Coenzyme.- F. Substrate Activity.- VI. Characteristics of Binding to PGDH.- A. The PG Site.- B. Comparison with Receptors for the Biological Actions of PGs.- C. The DPN+ Site.- VII. Reversibility of PGD.- VIII. Other Regulatory Factors.- IX. Enzymatic Assay of PGs.- X. Summary.- XI. References.- 5 Behavioral Effects.- I. Introduction.- II. Role of Prostaglandins in Brain Function.- III. Role of Prostaglandins in Neurotransmission.- IV. Metabolism of Prostaglandins in Brain.- V. Effects of Prostaglandins on Behavior.- VI. Effects of Prostaglandins on Body Temperature.- VII. Summary and Conclusions.- VIII. References.- 6 Embryonic and Fetal Development.- I. Introduction.- II. Action on the Early Conceptus.- A. Laboratory Animals.- B. Human Studies.- III. Teratogenicity Studies.- A. Teratogenic Influences.- B. Mammalian Species.- C. Chick Development.- D. Congenital Anomalies.- IV. Fetal Effects in Humans.- V. Prostaglandin-Progesterone Effects.- VI. Prostalandin-Synthetase Inhibitors.- VII. Prostaglandins and the Placenta.- A. Functional.- B. Morphological.- VIII. Conclusions.- IX. References.- 7 Search for Common Mechanisms Underlying the Various Effects of Putative Inflammatory Mediators.- I. Introduction.- II. Historical Background.- III. Actions of and Interactions Between Potential Mediators and Drugs.- A. Introduction.- B. Rat Paw Edema: Mechanisms of Induction and Inhibition and Hypothesized Role of Phospholipase A2.- C. Edema and Vascular Permeability Increase by Venoms.- D. Ultraviolet Erythema in Guinea Pigs and Lipoperoxidation during Inflammation.- E. Direct and Indirect Effects of Bradykinin.- F. Effects of Adenosine Nucleotides.- G. Effects of Arachidonic Acid and of Slow-Reacting Substance C.- H. Pharmacological Properties of a Few Substances Known to Induce Inflammation.- IV. Evidence from Studies on Anti-Inflammatory Drugs in Isolated Cell Systems.- A. Erythrocytes.- B. Mast Cells.- C. Platelets.- V. Summary and Conclusions.- VI. References.- 8 Immunology.- I. Introduction.- II. IgE-Mediated Release of Histamine and Other Mediators.- III. Lymphocyte Cytolytic Activity.- IV. The Humoral Antibody Response.- V. Neutrophil and Macrophage Function.- VI. Lymphocyte Proliferation.- VII. Speculation on Prostaglandins and the Immune Response.- VIII. References.- IX Site-Directed Mutagenesis.- Appendix A UV Spectral Characteristics and Acidic Dissociation Constants of Modified Bases, Nucleosides, and Nucleotides.- Appendix B Acid, Neutral, and Basic Spectra of Bases, Nucleosides, Nucleotides, and 55 Modified Derivatives.