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 (Fig. 20-5).
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 slow-reacting substance of anaphylaxis
(SRS-A), cause slow and sustained constriction of
the bronchioles and are important inflammatory mediators
in bronchial asthma and anaphylaxis.