Differential effects of prostaglandin E2 and cyclic AMP on release of arachidonic acid metabolites from resting and lipopolysaccharide-stimulated macrophages.

The present study investigated the effect of cyclic adenosine 3',5'-monophosphate (cyclic AMP) and prostaglandin E2 (PGE2) on arachidonic acid metabolism in rat peritoneal macrophages. Dibutyryl cyclic AMP (db-cyclic AMP) caused differential effects on the synthesis of PGE2 and thromboxane. Although db cyclic AMP enhanced the release of PGE2, it inhibited the release of thromboxane. This suggests that cyclic AMP may regulate cellular functions via induction of a shift in the proportion of arachidonic acid metabolites. PGE2, at low concentrations, markedly inhibited thromboxane release in nontreated macrophages, but it had virtually no effect on thromboxane release in cells treated with lipopolysaccharide (LPS). By contrast, db-cyclic AMP inhibited thromboxane release also in LPS-stimulated cells. The interrelationships between PGE2, thromboxane and cyclic AMP, and possible interference of LPS in these interactions are discussed.