Effect of inhibitors of arachidonic acid metabolism upon IgE and non-IgE-mediated histamine release.
Inhibitors of arachidonic acid metabolism were tested for their ability to block histamine release from human basophils. Eighteen inhibitors of lipoxygenases, cyclo-oxygenases, prostaglandin isomerases and thromboxane synthetases were tested. Agents inhibitory to the activity of lipoxygenases were effective blockers of IgE and non-IgE-mediated histamine release; agents antagonistic to cyclo-oxygenases, isomerases and thromboxane synthetases were not. These findings indicate that a functioning lipoxygenase pathway is essential for basophil activation and secretion and that the cyclo-oxygenase, isomerase and thromboxane synthetase pathways are not. Compounds antagonistic to phospholipase A also block histamine release, as does the intracellular Ca2+ antagonist TMB-8. The data are consistent with the idea that mast-cell and basophil activation and secretion involve phospholipase A generation of arachidonic acid, which is metabolized via the lipoxygenase pathway.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001491:Basophils / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D066298:In Vitro Techniques; D008407:Mast Cells / Q000201:enzymology; D010741:Phospholipases A / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D010741:Phospholipases A