Lipid metabolism during mediator release from mast cells: studies of the role of arachidonic acid metabolism in the control of phospholipid metabolism.
Recent studies indicate that both arachidonic acid (AA) metabolism and phospholipid (PL) metabolism are markedly stimulated during the release of mediators from mast cells. The relationship between stimulated AA metabolism and stimulated PL metabolism in isolated rat mast cells was investigated and then correlated with the secretory process. ETYA (5,8,11,14-eicosatetraynoic acid, a known inhibitor of cyclooxygenase and lipoxygenase pathways of AA metabolism) inhibited 32PO4 incorporation into phosphatidic acid (PA), phosphatidylinositol (PI), and phoshodidylcholine (PC) in both unstimulated mast cells and mast cells stimulated by cross-linking of surface IgE molecules. ID50 values for inhibition of mediator release and of basal and stimulated 32PO4 incorporation into PL were 50 to 60 microM ETYA. Indomethacin (1 to 10 microM) and aspirin (10 to 100 microM) had no significant effect on 32PO4 incorporation or on mediator release. AA (10 microM) inhibited PL labeling in resting mast cells and rendered the cells less responsive to secretory signals. Preincubation of the cells with indomethacin (1 microM) blocked both of these AA effects. When AA was added to stimulated mast cells, however, both PL labeling and mediator release were enhanced. Thus, each of the alterations in AA metabolism caused parallel changes in mast cell PL metabolism and in mediator release. Since both basal and stimulated PL metabolism were modified by ETYA and AA, some form of direct regulation of mast cell PL metabolism by AA metabolites seems likely. The close parallelism of effects on mediator release and on PL metabolism suggests that modulation of mast cell function by AA metabolites may be mediated at lest in part by effects on lipid metabolism.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D050356:Lipid Metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D009194:Myeloma Proteins / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats
D001095:Arachidonic Acids; D009194:Myeloma Proteins; D010743:Phospholipids; D015117:5,8,11,14-Eicosatetraynoic Acid; D001241:Aspirin; D007213:Indomethacin