PREVENTIVE EFFECTS OF THEOPHYLLINE ON ANAPHYLACTIC SHOCK IN RATS
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Anaphylactic shock was induced by administration of ovalbumin to sensitized rats. Preventive effects of theophylline on anaphylactic shock were examined with regard to the relationship between cyclic AMP and prostaglandin (PG) E<SUB>2</SUB> in lung tissue, and plasma histamine. During anaphylactic shock, levels of cyclic AMP content and PGE<SUB>2</SUB> content in lung tissue decreased, while plasma histamine content increased. Theophylline increased levels of cyclic AMP content and PGE<SUB>2</SUB> content in lung tissue, in a dose dependent manner, and pretreatment of animals with theophylline prevented the onset of anaphylactic shock. Pretreatment with indomethacin abolished the preventive effects of theophylline on anaphylactic shock, and the effect of theophylline on the cyclic AMP content. Dibutyryl cyclic AMP (DBcyclic AMP) increased PGE<SUB>2</SUB> content in lung tissue, in a dose dependent manner, and also prevented the onset of anaphylactic shock. These effects of DBcyclic AMP were inhibited by the pretreatment with indomethacin, and here, cyclic AMP in lung tissue was maintained at a high level. In the group in which anaphylactic shock was prevented with these interventions, PGE<SUB>2</SUB> content in lung tissue was significantly high in all cases. In addition PGE<SUB>2</SUB> infusion prevented anaphylactic shock. These data suggest that theophylline increases cyclic AMP levels in lung tissue only in the presence of endogenous PG, that increased cyclic AMP content in lung tissue subsequently increases PGE<SUB>2</SUB> content in lung tissue, and that the preventive effects of theophylline on anaphylactic shock result from increased PGE<SUB>2</SUB> content in lung tissue.
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