Interactions of arachidonic acid metabolites and platelet activating factor and mechanism of action in hypersensitivity reactions.
1. Sensitized guinea pig lungs release substantial amounts of prostaglandin E2, 6-keto-prostaglandin F1 alpha, thromboxane B2 and leukotrienes B4 and D4 upon challenge with the specific antigen. 2. A specific Platelet Activating Factor (PAF) antagonist (BN-52021) significantly inhibited the release of these mediators from anaphylactic lungs, suggesting the existence of interactions between PAF and eicosanoids. 3. The injection of PAF into unsensitized guinea pig lungs induced the release of prostaglandin E2, thromboxane B2 and leukotrienes B4 and D4 as well as spasmogens having contractile effects on the trachea, bronchus and parenchyma strips. 4. Our studies on the mechanism of action of PAF suggest that the actions of PAF are mediated by leukotriene B4 which in turn release thromboxane A2. Recent results suggest that similar interactions between PAF and eicosanoids are likely in immune-complex hypersensitivity reaction in the rat.
Jancar
S
S
Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Canada.
Braquet
P
P
Sirois
P
P
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D015232:Dinoprostone; D004224:Diterpenes; D004537:Eicosanoic Acids / Q000378:metabolism; D004789:Enzyme Activation; D046934:Ginkgolides; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D004224:Diterpenes; D004537:Eicosanoic Acids; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D011458:Prostaglandins E; D013189:SRS-A; D007975:Leukotriene B4; D013929:Thromboxane B2; C045856:ginkgolide B; D010740:Phospholipases; D010741:Phospholipases A; D015232:Dinoprostone