Evidence for lipoxygenase pathway involvement in allergic tracheal contraction.
Challenge of actively sensitized guinea-pig trachea in vitro led to a contraction which was enhanced by the cyclo-oxygenase inhibitors, indomethacin and sodium meclofenamate. Cyclo-oxygenase inhibitors eliminated the release of PGE-like material induced by arachidonic acid (AA), histamine, and antigen challenge. AA (10 microgram./ml.) and PGE2 (100 ng./ml.) usually relaxed the trachea, whereas in the presence of cyclo-oxygenase inhibitors a contraction occurred. Phenidone and ETYA, which also blocked the lipoxygenase pathway of AA metabolism inhibited the enhancement of allergic tracheal contraction induced by cyclo-oxygenase inhibitors, decreased the time that the trachea remained contracted, and also eliminated the contraction induced by AA and PGE2. Thus, cyclo-oxygenase inhibitors may enhance allergic tracheal contraction by diverting AA metabolism into the lipoxygenase pathway and product of the latter pathway, possibly SRS-A, may be responsible for the enhancement and for the prolonged phase of allergic tracheal contraction. An analogous mechanism may account for aspirin-induced asthma in man.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000209:etiology; D003251:Constriction, Pathologic; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006967:Hypersensitivity / Q000209:etiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D013189:SRS-A / Q000502:physiology; D014133:Tracheal Diseases / Q000209:etiology*
D001095:Arachidonic Acids; D011459:Prostaglandins E, Synthetic; D013189:SRS-A; D006632:Histamine; D008084:Lipoxygenase; D001241:Aspirin; D007213:Indomethacin