Anaphylactic responses of guinea-pig lung parenchymal strips: antigen concentration dependence and pharmacological...

The effects of mediator antagonists and synthesis inhibitors on anaphylactic responses of lung parenchymal strips from ovalbumin-sensitized guinea-pigs have been investigated. The dependence of the responses on the concentration of the antigen has been studied using a cumulative concentration-response technique. Anaphylactic contraction and histamine release were similar in response to cumulative and single additions of ovalbumin. Contractile responses to high doses of antigen (1 and 10 micrograms/ml) were slightly inhibited by mepyramine, whereas those to low doses (0.01 microgram/ml) were inhibited by leukotriene antagonist FPL 55712 and the lipoxygenase inhibitors nordihydroguaiaretic acid and BW 755C. Indomethacin potentiated both histamine release and contraction induced by ovalbumin. It is concluded that leukotrienes play a major role in anaphylactic responses to low antigen concentrations. Such responses may more closely resemble allergic bronchoconstriction in man. Histamine has a minor role in responses to higher antigen concentrations, where the major mediator of the responses may also be leukotrienes. This possibility cannot be proved with currently available leukotriene antagonists and synthesis inhibitors.