PAF STIMULATES CAMP FORMATION IN P388D(1) MACROPHAGE-LIKE CELLS VIA THE FORMATION AND SECRETION OF PROSTAGLANDIN E(2) IN AN AUTOCRINE FASHION

The role of cAMP in the formation of prostaglandin E(2) (PGE(2)) was i nvestigated in bacterial lipopolysaccharide (LPS)-primed P388D(1) macr ophage-like cells stimulated with platelet activating factor (PAF). cA MP levels and PGE(2) secretion were correlated with stimulation by PAF or ionomycin. Indomethacin inhibited cAMP formation induced by PAF, b ut not PGE(2)-stimulated cAMP production. Inositol (1,4,5)-trisphospha te levels were strongly reduced by exogenous PGE(2) and increased by H -89, an inhibitor of PKA. However, exogenous PGE(2) did not affect PAF -stimulated PGE(2) formation. These results suggest that cAMP levels i n P388D, cells are regulated by PGE(2) in an autocrine fashion. Eviden ce is presented that this feedback mechanism regulates inositol (1,4,5 )-triphosphate levels in these cells, while PGE(2) formation is not af fected.