Arachidonic Acid Metabolites.

Arachidonic acid is a 20- carbon unsaturated fatty acid found in

phospholipids of cell membranes. Release of arachidonic acid by phospholipases initiates a
series of complex reactions that lead to the production of prostaglandins, leukotrienes, and other
mediators of inflammation.
The synthesis of inflammatory mediators follows one of two pathways: the cyclooxygenase
pathway, which culminates in the synthesis of the prostaglandins, and the lipoxygenase pathway,
which culminates in the synthesis of the leukotrienes.
Several prostaglandins are synthesized from arachidonic acid through the cyclooxygenase
metabolic pathway. The stable prostaglandins (PGE1 and PGE2) induce inflammation
and potentiate the effects of histamine and other inflammatory mediators.
The prostaglandin thromboxane A2 promotes platelet aggregation and vasoconstriction. Aspirin
and the nonsteroidal antiinflammatory drugs (NSAIDs) reduce inflammation by inactivating the
first enzyme in the cyclooxygenase pathway for prostaglandin synthesis.
Like the prostaglandins, the leukotrienes are formed from arachidonic acid, but through the
lipoxygenase pathway. Histamine and leukotrienes are complementary in action in that they have
similar functions. Histamine is produced rapidly and transiently while the more potent
leukotrienes are being synthesized.
The leukotrienes also have been reported to affect the permeability of the postcapillary venules,
the adhesion properties of endothelial cells, and the chemotaxis and extravasation of neutrophils,
eosinophils, and monocytes. Leukotrienes C4, D4, and E4, collectively known as the slowreacting substance of anaphylaxis (SRS-A), cause slow and sustained constriction of the
bronchioles and are important inflammatory mediators in bronchial asthma and anaphylaxis.