EICOSANOID

EICOSANOID

1. cyclical route

   • The cyclic pathway is initiated by the action of prostaglandin lytase G/H, PGS (also called endoperoxid prostaglandin lytase). This enzyme has two activities, cyclooxygenase (COX) and peroxylase.
     • There are two forms of COX. (ENZYME)
       • COX-1 (PGS-1) is expressed constitutively in the gastric mucosa, kidneys, platelets, and vascular endothelial cells.
       • COX-2 (PGS-2) is an inducible enzyme and is expressed in macrophages and monocytes in response to inflammation. The most important stimuli for COX-2 induction in monocytes and macrophages is platelet activator factor, PAF and interleucine-1, IL-1.

2. linear route

   • The linear pathway is initiated by the action of lipooxygenase of which there are three forms, 5-LOX, 12 LOX and 15LOX. It is the enzyme, 5-lipooxygenase that results in leukotriene. Leukotriene are synthesized by different types of cells including leukocytes (hence the derivation of the name of these compounds), mast cells, lungs, spleen, brain and heart.

3. types general

   • PROSTAGLANDINS, THROMBOOXANES, LEUKOTRIENES

4. precursor

   • Gamma-linoleic acid (homo-gamma-linoleic acid) Arachydonic acid Eicosapentaenoic acid

5. Functions

   • LXA4
     • reduce PMNs and infiltrate eosinophils to inflammation sites, stimulate nonphlogistic (non-recruitment of induced inflammatory monocytes), stimulate the macrophages phagocytosis of PMN apoptosis, block IL-8 (chemokine) expression, block TNF-α release and actions, stimulate the action of TGF-β
   • PGI2
     • Inhibits platelet and leukocyte aggregation, decreases T cell proliferation and lymphocyte migration and excretion of IL-1a and IL-2; induces vasodilation and cAMP production
   • PGE1
     • induces vasodilation and inhibits platelet aggregation
   • PGE2
     • Increases vasodilation and cAMP production, increases the effects of bradycycin and histamine, induction of uterine contraction and platelet aggregation, keeps the arterious duct open in the fetus, decreases T-cell proliferation and migration of IL-1 and IL-2 lymphocytes
   • PGD2
     • induces inflammatory responses mainly by eosinophils and recruitment basophils, induces bronchoconstriction, involved in androgenetic alopecia, PGD2 inhibitors under study to treat male pattern baldness
   • TXA2
     • Induces platelet aggregation, vasoconstriction, lymphocyte proliferation and bronchoconstriction