Five-Lipoxygenase Products in Asthma PDF

PREFACE

In 1938, Kellaway and Trethewey, working in Australia, identified a material in the effluent of anaphylactic guinea pig lungs, which they termed ‘‘slow-reacting substance'' (SRS) because it elicited constriction of isolated guinea pig ileum in a manner that was slower and harder to reverse than that induced by histamine. Almost two decades later, Brockelhurst provided very clear evidence that SRS was not histamine since the newly discovered antihistamines did not inhibit its action. More importantly, over the period from 1956 to 1979, it was demonstrated that slow-reacting substance, derived from anaphylactic exudates, was an extremely potent and unique airway smooth muscle contractile material. This material was called ‘‘slow-reacting substance of anaphylaxis'' (SRS-A).

In 1979, Robert Murphy, working in Bengt Samuelsson's laboratory, described the chemical structure of SRS-A as the leukotrienes and defined the major arms of the 5-lipoxygenase pathway. Over the ensuing 18 years, a worldwide research effort was launched to (1) define the molecular biology, cell biology, and physiology of the leukotrienes; (2) find agents that inhibited the synthesis or action of the leukotrienes; and (3) show that such agents were able to provide a salutary therapeutic effect in patients with asthma.

This book provides a state-of-the-art review of our understanding of the 5-lipoxygenase pathway and, more importantly, of how it can be specifically interrupted to provide a therapeutic effect in asthma. Part I reviews in detail the basic science of the 5-lipoxygenase pathway and its cell and molecular biology. In Part II, clinical applications with respect to inhibiting the 5-lipoxygenase pathway are reviewed. A unique feature of this volume is that it provides concise and comprehensive reviews of each of the available pharmacological agents acting on the 5-LO pathway used in the treatment of asthma.

This book will be of value to researchers who need to obtain the most current information on the 5-lipoxygenase pathway, as well as to clinicians who wish to use these products to provide the most up-to-date asthma therapy.