Repeatable antigen-induced contractions of isolated guinea pig lung strips are mediated by leukotriene

Lung strips from actively sensitized guinea pigs were repeatedly contracted by antigen (ovalbumin, OA) challenge in the presence of the antihistamine (H1) mepyramine. At lower concentrations of OA, hourly challenges gave reproducible and consistent responses. High-concentration OA resulted in desensitization, with two to six contractions being very weak. The antigen concentration affected not only the force of contraction, but other parameters including the time to peak effect, the protraction of the peak effect, and the repeatability of the force and time to peak. Low concentrations of OA induced a response which peaked by 6-8 min and decreased by about 30% after 15 min, while high-concentration OA resulted in a contraction which peaked later and did not relax. These data suggest that different 'early' and 'late' mediators may be involved depending on the 'activation state' or the mechanisms that predominate in the contraction response as a result of the amount of stimulation by antigen. Leukotriene apparently mediates the peak and the 15-min contraction since both were inhibited completely by FPL-55712 (IC50 = 8 microM) or NDGA (IC50 = 5 microM). These repeated, leukotriene-mediated contractions of isolated lung may mimic the clinical situation (chronic exposure to low amounts of antigen) of allergic disease and may be used to study the modulation of lung responses and desensitization phenomena.