Characterization of platelet activating factor (PAF)-acether-induced contractions of guinea-pig lung strips by selected inhibitors of arachidonic acid metabolism and by PAF-acether antagonists.
The myotropic activities of PAF-acether, leukotriene B4, leukotriene D4 and histamine were compared on superfused guinea-pig lung parenchymal strip and were shown to have the following order of potency: PAF-acether greater than LTD4 greater than LTB4 greater than histamine. The contractile response of the lung parenchyma to PAF-acether was inhibited by aspirin, imidazole and OKY-046, which suggested that thromboxane A2 might play a mediator role in PAF-induced contractions. Neither an antagonist of leukotriene D4, FPL-55712, nor an antihistamine, mepyramine, had any effect on PAF contractions. The activity of a novel antagonist of PAF-acether, BN 52021, was also studied on superfused lung parenchyma contracted by histamine, leukotriene B4, leukotriene D4 and PAF-acether. This compound was without effect on the histamine response but it slightly reduced the contractions elicited by leukotriene D4 and potentiated those by leukotriene B4. BN 52021 (7.1 X 10(-6) M) inhibited by 63% the contraction induced by 5.7 X 10(-13) M PAF-acether and by 52% that induced by 5.7 X 10(-10) M PAF-acether and kadsurenone (8.4 X 10(-6) M), another PAF-acether antagonist, inhibited the same PAF-induced contractions by 75% and 20% respectively.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007783:Lactones; D007975:Leukotriene B4 / Q000494:pharmacology; D017705:Lignans; D008168:Lung / Q000187:drug effects*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology
D001572:Benzofurans; D002867:Chromones; D004224:Diterpenes; D046934:Ginkgolides; D007093:Imidazoles; D007783:Lactones; D017705:Lignans; D008689:Methacrylates; D010936:Plant Extracts; D010972:Platelet Activating Factor; D011448:Prostaglandin Antagonists; D013189:SRS-A; D007975:Leukotriene B4; C029899:imidazole; D006632:Histamine; C006312:FPL 55712; C044540:kadsurenone; C045856:ginkgolide B; D011738:Pyrilamine; C034364:ozagrel; D001241:Aspirin