Eicosanoids and Regulators

Eicosanoids are a family of compounds derived from polyunsaturated eicosanoic acids. The eicosanoids include prostaglandins, leukotrienes, and the intermediate hydroperoxyeicosatetraenoic (HPETE) and hydroxyeicosatetraenoic (HETE) acids. The prostaglandins and leukotrienes act as paracrine and autocrine regulators, through a family of transmembrane receptors. Signaling through these receptors allows prostaglandins and leukotrienes to regulate a variety of physiological and pathophysiological processes.

Prostaglandin E2 (PGE2) is formed in a variety of cells from prostaglandin H2, which is synthesized from arachidonic acid by the enzyme prostaglandin synthetase. PGE2 has a number of biological effects, including vasodilation, modulation of sleep/wake cycles, facilitation of human immunodeficiency virus replication, and both anti- and pro-inflammatory effects. PGE2 elevates cAMP levels, stimulates bone resorption and has thermoregulatory effects. PGE2 has also been shown to be a regulator of sodium excretion and renal hemodynamics.

Leukotriene B4 (LTB4) is a major product of arachidonic acid metabolism and is formed via the 5-lipoxygenase pathway. LTB4 stimulates leukocyte functions including lysosomal enzyme release, adhesion, and aggregation of polymorphonuclear leukocytes. LTB4 exerts it effects via the Leukotriene B4 Receptor 1 (LTB4R1), a seven transmembrane G protein-coupled receptor that is highly expressed in lymphoid tissues. LTB4 has been implicated as a potent mediator of inflammatory diseases and immunoregulation.