Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E-2

The two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, bot h metabolize arachidonic acid to prostaglandin H-2, which is subsequently p rocessed by downstream enzymes to the various prostanoids. In the present s tudy, we asked if the two isoforms differ in the profile of prostanoids tha t ultimately arise from their action on arachidonic acid. Resident peritone al macrophages contained only cyclooxygenase-1 and synthesized (from either endogenous or exogenous arachidonic acid) a balance of four major prostano ids: prostacyclin, thromboxane A(2), prostaglandin D-2, and 12-hydroxyhepta decatrienoic acid. Prostaglandin E-2 was a minor fifth product, although th ese cells efficiently converted exogenous prostaglandin H-2 to prostaglandi n E-2. By contrast, induction of cyclooxygenase-a with lipopolysaccharide r esulted in the preferential production of prostacyclin and prostaglandin E- 2. This shift in product profile was accentuated if cyclooxygenase-1 was pe rmanently inactivated with aspirin before cyclooxygenase-2 induction. The c onversion of exogenous prostaglandin H-2 to prostaglandin E-2 was only mode stly increased by lipopolysaccharide treatment. Thus, cyclooxygenase-a indu ction leads to a shift in arachidonic acid metabolism from the production o f several prostanoids with diverse effects as mediated by cyclooxygenase-1 to the preferential synthesis of two prostanoids, prostacyclin and prostagl andin E-2, which evoke common effects at the cellular level.