Physiological and pathophysiological activities of leukotrienes

Abstract

Studies of the metabolism of arachidonic acid by leukocytes in the late 1970s led to the discovery of the leukotriene (LT) family with its principal members, the dihydroxy acid leukotriene B4 (LTB4) and the cysteinyl leukotrienes C4, D4 and E4 (LTC4, LTD4, LTE4), and the identification of slow-reacting substance of anaphylaxis (SRS-A) as a mixture of the latter LTs [1-2]. Throughout its many years as a powerful smooth muscle stimulant of unknown chemical structure, SRS-A remained an intriguing entity, possibly implicated as mediator of hypersensitivity reactions, in particular those concerned with allergic asthma. Elucidation of the chemical structure of SRS-A, and the realization that it was not a single substance but rather a mixture of interrelated LTs, necessitated reappraisal of earlier data on the effects of SRS-A in pulmonary tissue. Furthermore, as the LT family grew larger, interest turned also to other tissues and organ systems, with the ultimate goal of disclosing specific targets for the different LTs. It is now generally accepted that the LTs collectively provoke contraction of vascular and nonvascular smooth muscle, increased vascular permeability, and accumulation and activation of leukocytes. The LTs often operate with a potency which far exceeds that of traditional autacoids, and they have obvious key targets of action within the pulmonary and cardiovascular systems, and on cells involved in nonspecific defense and immune regulation. It has been conclusively documented that LTs are important mediators in bronchial asthma (see chapter by Dahlén, this volume), and data are accumulating to indicate that they are involved in a number of other disease states, such as rhematoid arthritis, inflammatory bowel disease, glomerulonephritis, psoriasis and cardiac disorders [3-4].KeywordsHypoxic Pulmonary VasoconstrictionPlasma LeakageHamster Cheek PouchProstaglandin Leukot Essent Fatty AcidPathophysiological ActivityThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.