Toxic oxygen products alter calcium homeostasis in an asthma model

After anaphylactic or synthetic leukotriene C4 contractions in guinea pig trachealis muscle, an accelerated initial rate and greater total myorelaxation are induced in these muscle preparations when they are immersed in calcium-free medium, O(Ca++)E. Inhibition of the late phase of anaphylaxis (ANA) by FPL 55712 (10(-5) mol/L) eliminated the post-ANA O(Ca++)E-augmented myorelaxation, suggesting a causal role for SRS-A products. Hypoxia or superoxide dismutase/catalase pretreatment also abolished the post-ANA or leukotriene C4 O(Ca++)E-augmented myorelaxation. The data support the hypothesis that toxic oxygen products generated with SRS-A and/or LTC4 induce an alteration in Ca++ homeostasis in airway smooth muscle. In this model of allergic asthma, airway smooth muscle alteration after ANA may contribute to the pathogenesis of asthma and/or airway hypersensitivity associated with allergic asthma.