Stimulation of the antigen-induced contraction of guinea-pig trachea and immunological release of histamine and SRS-A from sensitized guinea-pig lung by (2-isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin.
1 (2-Isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin reduced basal tension and enhanced the antigen- and histamine-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. The stimulating effect of L8027 required the presence of the drug, while that of indomethacin persisted after its removal from the organ bath. 2 L8027 and indomethacin stimulated the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) and inhibited the de novo synthesis and release of malondialdehyde from actively sensitized guinea-pig lung fragments. 3 L8027 was 2,800 times more potent than indomethacin in both in vitro models of anaphylaxis. 4 A selective antagonist of SRS-A (FPL 55712) inhibited contractions produced by antigen, but had no effect on contractions produced by histamine. 5 Prostaglandins E and F2 alpha were continuously released into the organ bath fluid by the resting trachea. Contractions induced by antigen or histamine increased the rate of prostaglandin efflux. 6 L8027 had no effect on the efflux of prostaglandins E and F2 alpha at rest and during contraction. Indomethacin inhibited prostaglandin efflux at rest and during contraction while present in the organ bath. Prostaglandin efflux was restored to 80% of control after removal of indomethacin. 7 The results suggest that prostaglandins E and F2 alpha have no role in the stimulation by L8027 and indomethacin of the contractile responses of guinea-pig trachea. The possible mechanism for the effects of these drugs is discussed.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D000941:Antigens; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011453:Prostaglandins / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013189:SRS-A / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000378:metabolism
D000941:Antigens; D007211:Indoles; D011453:Prostaglandins; D011725:Pyridines; D013189:SRS-A; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; C002092:nictindole; D007213:Indomethacin