A glycerol ether induces mobilization and 12-lipoxygenation of arachidonic acid in macrophages. Synergistic effect on mobilization and induction of leukotriene C formation by activators of protein kinase C.
A glycerol triether, 1,2-isopropylidene 3-0-decanyl-sn-glycerol, was found to induce mobilization of arachidonic acid from ethanolamine phosphoglycerides and phosphatidylinositol in mouse peritoneal macrophages. This effect showed structural specificity, occurred without activation of protein kinase C and resulted in formation and release of predominantly 12-hydroxy-eicosatetraenoic acid. Activators of kinase C (4-beta-phorbol 12-myristate 13-acetate and 1,2-dioctanoyl-sn-glycerol) instead specifically enhance prostaglandin E2 formation. When macrophages were exposed to both a kinase C activator and the glycerol triether, the mobilization of arachidonic acid was synergistically enhanced and formation of leukotriene C was induced.
Sundler
R
R
Department of Medical and Physiological Chemistry, University of Lund, Sweden.
Emilsson
A
A
Wijkander
J
J
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013189:SRS-A / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D004075:Diglycerides; D005995:Glyceryl Ethers; D006893:Hydroxyeicosatetraenoic Acids; D010750:Phosphoproteins; D013189:SRS-A; C044295:1,2-dioctanoylglycerol; D016718:Arachidonic Acid; C058203:1,2-isopropylidene-3-decanoylglycerol; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases; D001092:Arachidonate 12-Lipoxygenase; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate