PAF stimulates cAMP formation in P388D1 macrophage-like cells via the formation and secretion of prostaglandin E2 in an autocrine fashion.
The role of cAMP in the formation of prostaglandin E2 (PGE2) was investigated in bacterial lipopolysaccharide (LPS)-primed P388D1 macrophage-like cells stimulated with platelet activating factor (PAF). cAMP levels and PGE2 secretion were correlated with stimulation by PAF or ionomycin. Indomethacin inhibited cAMP formation induced by PAF, but not PGE2-stimulated cAMP production. Inositol (1,4,5)-trisphosphate levels were strongly reduced by exogenous PGE2 and increased by H-89, an inhibitor of PKA. However, exogenous PGE2 did not affect PAF-stimulated PGE2 formation. These results suggest that cAMP levels in P388D1 cells are regulated by PGE2 in an autocrine fashion. Evidence is presented that this feedback mechanism regulates inositol (1,4,5)-triphosphate levels in these cells, while PGE2 formation is not affected.
Asmis
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Department of Chemistry, University of California, San Diego, La Jolla 92093-0601.
Dennis
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EA
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015398:Signal Transduction; D013449:Sulfonamides
D016861:Cyclooxygenase Inhibitors; D007546:Isoquinolines; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D013449:Sulfonamides; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide