EFFECTS OF SELECTED ANTAGONISTS ON OVALBUMIN-INDUCED CONTRACTION OF TRACHEAL STRIPS ISOLATED FROM THE ACTIVELY SENSITIZED GUINEA-PIG

Tracheal strips were obtained from guinea pigs actively sensitized with egg albumin (ovalbumin). The dose-response curve to ovalbumin was not altered by phenoxybenzamine or mepyramine in concentrations adequate to antagonize dose-response effects of histamine snd Compound 48/80, a histamine releasing substance. FPL55712, an antagonist of slow reacting substance of anaphylaxis (SRS-A), produced a 7-fold shift to the right of the ovalbumin dose-response curve at a concentration 100 times that requires to produce an approximate 10-fold shift of the dose-response effects of exogenously applied SRS-A. Combination of a histamine receptor anatagonist (phenoxybenzamine or mepyramine) with large concentrations of FPL55712 (10-5 and 10-4 M) markedly antagonized the ovalbumin-induced tracheal contraction. Indomethacin enhanced the contractions produced by all concentrations of ovalbumin and this effect was prevented by 5, 8, 11, 14-eicosatetraynoic acid (TYA). TYA alone produced a 4-fold shift to the right of the ovalbumin dose-response curve. Combination of a histamine receptor antagonist with TYA resulted in a marked antagonism of the ovalbumin-induced tracheal contraction. The data suggest that antigen produces tracheal smooth muscle contraction via more than one released mediator. One of the mediators is suggested to be histamine and another a metabolite, or a substance whose release is controlled by a metabolite, of arachidonic acid; possibly SRS-A. Comparison of the data with theoretical dose-response curves calculated from a model for functional synergism suggest that the anaphylactic tracheal contraction involves more than an interaction between two aganist acting at their own specific receptors. Data with indomethacin and TYA are consistent with suggestions that indomethacin enhances antigen-induced effects by increasing metabolism of arachidonic acid via the lipoxygenase pathway. © 1979.