Prostaglandin synthase-1 and prostaglandin synthase-2 are coupled to distinct phospholipases for the generation of prostaglandin D2 in activated mast cells.
Aggregation of IgE cell surface receptors on MMC-34 cells, a murine mast cell line, induces the synthesis and secretion of prostaglandin D2 (PGD2). Synthesis and secretion of PGD2 in activated MMC-34 cells occurs in two stages, an early phase that is complete within 30 min after activation and a late phase that reaches a maximum about 6 h after activation. The early and late phases of PGD2 generation are mediated by prostaglandin synthase 1 (PGS1) and prostaglandin synthase 2 (PGS2), respectively. Arachidonic acid, the substrate for both PGS1 and PGS2, is released from membrane phospholipids by the activation of phospholipases. We now demonstrate that in activated mast cells (i) secretory phospholipase A2 (PLA2) mediates the release of arachidonic acid for early, PGS1-dependent synthesis of PGD2; (ii) secretory PLA2 does not play a role in the late, PGS2-dependent synthesis of PGD2; (iii) cytoplasmic PLA2 mediates the release of arachidonic acid for late, PGS2-dependent synthesis of PGD2; and (iv) a cytoplasmic PLA2-dependent step precedes secretory PLA2 activation and is necessary for optimal PGD2 production by the secretory PLA2/PGS1-dependent early pathway.
Reddy
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ST
Departments of Biological Chemistry and Molecular and Medical Pharmacology, and the Molecular Biology Institute, UCLA Center for the Health Sciences, Los Angeles, California 90095, USA.
Herschman
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HR
D000818:Animals; D000911:Antibodies, Monoclonal; D001095:Arachidonic Acids / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D063065:Organophosphonates / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001095:Arachidonic Acids; D007527:Isoenzymes; D063065:Organophosphonates; D017455:Receptors, IgE; C095801:SB 203347; D013449:Sulfonamides; C104810:methyl arachidonylfluorophosphonate; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D015230:Prostaglandin D2