SPECIFICITY OF EXPRESSION AND EFFECTS OF EICOSANOID MEDIATORS IN NORMAL PHYSIOLOGY AND HUMAN-DISEASES

The eicosanoids are a family of oxygenated arachidonic acid derivative s that potently mediate diverse physiological and pathophysiological p rocesses. Recent research on eicosanoids has revealed novel pathways o f synthesis, a family of related cell membrane receptors, and distinct ive roles in cellular functions. There are two cyclooxygenases that co nvert arachidonic acid to thromboxane and prostaglandins, one of which is localized in the endoplasmic reticulum and the other in the nuclea r envelope. The cyclooxygenases differ in their susceptibility to inhi bition by nonsteroidal antiinflammatory drugs. The leukotriene-generat ing pathway consists of a cytosolic perinuclear 5-lipoxygenase, two in tegral nuclear envelope proteins, termed 5-lipoxygenase-activating pro tein and LTC4 synthase, and a cytosolic LTA4 hydrolase. Each protein o f the leukotriene synthetic pathway is a target for specific pharmacol ogical intervention. Cellular recognition and effects of eicosanoids a re mediated by at least 12 different G protein-associated primary rece ptors, which differ in tissue distribution, signaling mechanisms, and cellular behavior, as well as binding specificity. Transient localized increases in tissue concentrations of eicosanoids and the concurrent upregulation of complementary receptors influence differentiation, mig ration, and specific activities of cells in immunity and other integra ted physiological responses.