The Leukotrienes

Chemistry and Biology

1st Edition - January 28, 1984
Editor: Lawrence Chakrin
Language: English
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 1 5 6 0 7 - 3

The Leukotrienes, Chemistry and Biology discusses the significant scientific progress of leukotrienes, from the discovery of slow-reacting substance to the chemical identification… Read more

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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.

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 ω 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