ABSTRACT
Many cells, if not all, release arachidonic acid when they are stimulated by hormones, neurotransmitters, antibodies, and other ligands. As described in other chapters, this fatty acid is further metabolized by the two pathways; leukotrienes and hydroxyperoxides of arachidonic acid are formed by the lipoxygenase pathway, while prostaglandins and thromboxanes are synthesized via the cyclooxygenase pathway. These metabolites of arachidonic acid have a variety of biological activities in inflammation, immunoregulation, neural activities, etc. Arachidonic acid does not exist as a free fatty acid in most cells; rather, it is esterified in the 2-position of various phospholipids. The generation or release of free arachidonic acid from phospholipids by the actions of phospholipases or other acylhydrolases is then a rate-limiting step for the formation of the biologically active metabolites such as prostaglandins and leukotrienes. Therefore, drugs which inhibit release of arachidonic acid from phospholipids can reduce the production of these metabolites and consequently modulate various biological activities. In this chapter the mechanism of actions of such drugs will be discussed.
