Roles of Lipases in the Development of Autonomic Neurons

Abstract

Glucocorticoids are widely used as therapeutics for immunological and inflammatory diseases (Sayers and Travis, 1970). This anti-inflammatory action of glucocorticoids is now proposed to be associated with the inhibition of the release of arachidonic acid, a precursor of inflammatory agents such as prostaglandins and leukotrienes (Blackwell et al., 1978). Arachidonic acid is mostly present in an esterified form rather than as a free fatty acid. Thus, the rate limiting step of the arachidonate release from intact cells is the activation of phospholipase A₂ or phospholipase C. Furthermore, this anti-inflammatory action of glucocorticoids can be blocked by the previous treatment with cycloheximide and actinomycin D, inhibitors of protein and RNA syntheses, respectively (Hirata et al., 1985b). From these observations, one can assume that glucocorticoids induce the synthesis of a protein(s) which inhibits cellular phospholipases. Recently, the four groups (Flower’s group in England, Russo-Marie’s group in France, and Goldberg’s group and our group in USA) have partially purified and characterized such a factor(s) and named this protein as lipocortin (DiRosa et al., 1984). Isolated lipocortin can suppress the carageenin-induced paw edema, an animal model of acute inflammation, and can inhibit the release of arachidonic acid from various intact cells. Thus, it has been proposed that the inhibition of phospholipases A₂ by lipocortin might be the main mechanism of the anti-inflammatory action of glucocorticoids (Hirata et al., 1985b).