title: The mechanism of enhancement by fatty acid hydroperoxides of anaphylactic mediator release.
abstract: Indomethacin augmented the release of histamine and SRS-A but abolished synthesis of TxB2. Compound CLI that inhibited both cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism did not augment release of anaphylactic mediators. 13-HPLA enhanced mediator release from lungs in which arachidonic acid metabolism was blocked by compount CLI. Thus, it is concluded that 13-HPLA enhances mediator release not by altering the balance of arachidonic acid metabolites, e.g. by inhibiting synthesis of prostacyclin, but by a direct effect on lung mast cells. A corollary to this conclusion is that the fatty acid hydroperoxide (HPETE) formed by lipoxygenase from arachidonic acid may also augment the release of anaphylactic mediators. Thus, the enhancement of mediator release by indomethacin may be attributed to increased synthesis of HPETE following inhibition of cyclo-oxygenase.
mesh_terms: D000707:Anaphylaxis; D000818:Animals; D000941:Antigens; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010105:Oxygenases / Q000037:antagonists & inhibitors; D010477:Perfusion; D013189:SRS-A / Q000378:metabolism*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D000941:Antigens; D001095:Arachidonic Acids; D008041:Linoleic Acids; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D013929:Thromboxane B2; D011464:Epoprostenol; D010105:Oxygenases; D007213:Indomethacin