The Leukotrienes

The Leukotrienes, Chemistry and Biology discusses the significant scientific progress of leukotrienes, from the discovery of slow-reacting substance to the chemical identification of a mixture of leukotrienes. Composed of 11 chapters, the book presents an enormous increase in research on the chemistry and biology of these and related substances, especially as they relate to the etiology of allergic and inflammatory diseases.
After briefly discussing the continuing perspectives on the leukotriene biology, the book describes the structure, synthesis, formation, and biological actions of leukotrienes. This is followed by a discussion on arachidonic metabolism for the development of therapeutic agents specifically designed to either inhibit the synthesis or antagonize the effects of the leukotrienes. The book also looks into the biochemical and pharmacologic control of the synthesis and actions of leukotrienes. The information is considered in the context of the specific enzymes in the pathway that may be affected by any given agent. The in vivo studies on the pulmonary mechanical effect of leukotrienes, the pharmacologic activity of leukotriene receptors, and the antagonistic property of peptidoleukotrienes as an approach to allergic disease treatment are considered in the concluding chapters of the book.
This book will be of value to scientists and researchers interested in hypersensitivity reactions, inflammation, and allergic diseases.

Contenu

Contributors

Preface

1. Historical and Continuing Perspectives on the Biology of the Leukotrienes

   I. Introduction

   II. Isolation and Characterization of SRS-A

   III. Recognition of the Components of SRS-A, the Leukotrienes

   IV. Studies of Target Tissue Responses

   V. Clinical Pharmacology

   References

2. Structure Elucidation and Total Synthesis of the Leukotrienes

   I. Introduction

   II. Discovery of the Leukotrienes

   III. Structure Elucidation and Synthesis of SRS-A

   IV. Trienic Isomers of LTA4 and LTC4

   V. Additional Syntheses of LTA4 and Diastereomers

   VI. Synthesis of Leukotriene B4 and Its Isomers

   VII. Synthesis of Leukotriene Analogs-Modification of the Portion of Leukotrienes

   VIII. Synthesis of Structural Analogs of Leukotrienes C4, D4, and E4-Modification of the Polar Region

   IX. Synthesis of LTB4 Analogs

   X. Novel Leukotrienes

   References

3. Platelet Arachidonate Lipoxygenase

   I. Introduction

   II. Platelet Lipoxygenase (Arachidonate: Oxygen Oxidoreductase)

   III. Inhibitors

   IV. Effects of Lipoxygenase Products on Platelets

   References

4. The Lipoxygenases in Leukocytes and Other Mammalian Cells

   I. General Features

   II. Lipoxygenases in Mammalian Tissues

   III. 5-Lipoxygenase Products

   IV. Kinetics of 5-Lipoxygenase Product Formation in Activated Cells

   V. Characterization of the 5-Lipoxygenase Enzyme in RBL-1 Cells

   References

5. Characterization of Leukotriene Formation

   I. Introduction

   II. Calcium Stimulation of the 5-Lipoxygenase

   III. Requirement of Reduced Glutathione

   IV. Subcellular Localization of Leukotriene-Forming Enzymes

   V. Kinetic Studies of 5-HETE, LTA4, and LTB4 Synthesis

   VI. Substrate Specificity for Leukotriene Formation via the 5-Lipoxygenase

   VII. Effect of Various Acetylenic Fatty Acids on Leukotriene Formation

   VIII. Summary and Conclusion

   References

6. Inhibitors of Leukotriene Synthesis and Action

   I. Introduction

   II. Nonselective Inhibitors

   III. Selective Inhibitors

   IV. Concluding Remarks

   References

7. Lipoxygenase Products: Mediation of Inflammatory Responses and Inhibition of Their Formation

   I. Introduction

   II. Metabolism of Arachidonic Acid

   III. Pathophysiological Properties of Lipoxygenase Products

   IV. Formation of Leukotrienes in Various Tissues

   V. Lipoxygenase Inhibition and Its Consequences

   VI. Conclusions

   References

8. Biological Actions of the Leukotrienes

   I. Introduction

   II. Leukotriene B4 and Leukotrienes with Amino Acid Residues at C-6

   III. Pharmacological Actions of the Leukotrienes

   IV. Conclusions

   References

9. Biochemical and Cellular Characteristics of the Regulation of Human Leukocyte Function by Lipoxygenase Products of Arachidonic Acid

   I. Generation and Degradation of Lipoxygenase Products of Arachidonic Acid in Leukocytes

   II. Regulation of Lipoxygenase Pathways by Endogenous Factors and Pharmacological Agents

   III. Lipoxygenase Products of Arachidonic Acid as Mediators of PMN-Leukocyte and Monocyte Function

   IV. Interactions of Lipoxygenase and Cyclooxygenase Products of Arachidonic Acid in the Modulation of PMN-Leukocyte Function

   V. Lipoxygenase Products of Arachidonic Acid as Intracellular Functional Constituents

   VI. Lipoxygenase Products of Arachidonic Acid as Mediators of T-Lymphocyte Function

   References

10. Pulmonary Pharmacology of the Leukotrienes

    I. Slow-Reacting Substance of Anaphylaxis (SRS-A)

    II. The Structure and Biosynthesis of Leukotrienes

    III. Leukotrienes and the Lung

    IV. Leukotriene Analogs

    V. Conclusions

    References

11. Pharmacologic Antagonism of the Leukotrienes

    I. Introduction

    II. Pharmacologic Approaches to Studying Receptors

    III. Leukotriene Receptors

    IV. Antagonism of Peptidoleukotrienes as an Approach to the Treatment of Allergic Diseases

    References

Index