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.