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Bronchial anaphylaxis in actively sensitized Sprague Dawley rats: studies on mediators involved
Abstract:
Previous experiments have shown that SD rats actively sensitized to ovalbumin (OA) undergo bronchial anaphylaxis at intravenous challenge with a specific antigen. The inhibitory effect of antiallergic drugs in this experimental system and the relation of the response to serum reaginic antibody levels, depend on sensitization conditions (Dahlbäck 1981; Dahlbäck et al. 1982). The present experiments indicate that the main primary mediators of the respiratory anaphylaxis are serotonin and product(s) of the cyclooxygenase pathway of arachidonic acid metabolism. This is the case whether the animals are sensitized with 10 or 100 micrograms OA together with 100 mg alum and whether they are examined 2-3 or 5-6 weeks after sensitization. However, the bronchoconstrictory efficacy of exogenously added 5-HT varies with the immunization conditions of the animals: those given 100 micrograms OA together with alum are more reactive to 5-HT at intravenous challenge than animals given 10 micrograms AO and alum. Moreover, compounds known to affect the lipoxygenase pathway of arachidonic acid metabolism influence the bronchial anaphylactic reaction in different ways depending on immunization and test conditions. These data suggest that 5-HT and some not yet identified product(s) of cyclooxygenase/thromboxane synthetase are main mediators of allergen-induced bronchial anaphylaxis in the rat and that products of the lipoxygenase pathway play a minor direct role but may modulate the response.