Diacylglycerol induces deacylation of phosphatidylinositol and mobilization of arachidonic acid in mouse macrophages. Comparison with induction by phorbol diester.
1,2-Dioctanoyl-sn-glycerol (2-50 microM) was found, like phorbol myristate acetate (greater than or equal to 3 nM) to stimulate phospholipase A-type cleavage of phosphatidylinositol and the release of arachidonic acid from macrophage phospholipids. The 1,3 isomer of dioctanoylglycerol was inactive, whereas racemic 1,2-dioctanoylglycerol was half as potent as the 1,2-sn enantiomer. Dioctanoylglycerol-induced deacylation of phosphatidylinositol was only partly dependent on extracellular calcium but was more severely inhibited by depletion of intracellular calcium. Chlorpromazine inhibited the deacylation of phosphatidylinositol, whereas inhibitors of cyclo-oxygenase and lipoxygenase were ineffective. Since both phorbol myristate acetate and 1,2-dioctanoyl-sn-glycerol are known to activate protein kinase C, the results suggest that this kinase is involved in the sequence of events leading to release of arachidonic acid in macrophages.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005989:Glycerides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D004075:Diglycerides; D005989:Glycerides; D010716:Phosphatidylinositols; D010743:Phospholipids; C044295:1,2-dioctanoylglycerol; D016718:Arachidonic Acid; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D002746:Chlorpromazine