EFFECTS OF INHIBITORS OF ANAPHYLACTIC MEDIATORS IN TWO MODELS OF BRONCHIAL ANAPHYLAXIS IN ANAESTHETIZED GUINEA‐PIGS

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Abstract
The effects of pretreatment with various inhibitors of anaphylactic mediators on antigen‐induced bronchoconstriction were studied in anaesthetized guinea‐pigs, actively sensitized according to two different regimens (one producing IgE‐ and IgG‐like antibodies and the other producing exclusively IgG antibodies). The phospholipase A2‐inhibitors mepacrine and p‐bromphenacylbromide caused a dose‐dependent inhibition of the antigen‐induced bronchoconstriction in guinea‐pigs sensitized to produce both IgE and IgG antibodies. No effect was seen in those sensitized to produce only IgG antibodies. In both models indomethacin pretreatment led to an increased anaphylactic bronchoreactivity, whereas mepyramine and FPL 55712 reduced it. BW 755C significantly reduced antigen‐induced bronchoconstriction in guinea‐pigs sensitized to produce both IgE and IgG antibodies. In this model, the residual bronchoconstriction evident after combined pretreatment with indomethacin and mepyramine was prevented by additional pretreatment with mepacrine, FPL 55712 or budesonide. Arachidonic acid given intravenously caused a marked bronchoconstriction that was prevented by indomethacin but not by budesonide, FPL 55712 or p‐bromphenacylbromide. Although the same pattern of anaphylactic mediators is released in the two models of anaphylactic bronchoconstriction, a different activation mechanism is indicated by the results obtained with phospholipase A2 inhibitors.