An in vivo model for measuring antigen-induced SRS-A-mediated bronchoconstriction and plasma SRS-A levels in the guinea-pig.
1 Pharmacological modulation of antigen-induced anaphylaxis in actively sensitized guinea-pigs with intravenously administered indomethacin (10 mg/kg), pyrilamine (2.0 mg/kg) and propranolol (0.1 mg/kg) resulted in a delayed onset, slowly developing bronchoconstriction indicative of a slow-reacting substance of anaphylaxis (SRS-A) response. 2 Measurements of pulmonary mechanics on the drug-pretreated animals challenged with ovalbumin demonstrated a more prominent effect on dynamic compliance than resistance. This is consistent with the more potent effects of SRS-A on peripheral rather than central airways. 3 The slowly developing bronchoconstriction obtained after treatment with indomethacin, pyrilamine and propranolol was inhibited by the standard SRS-A antagonist, FPL 55712 and the SRS-A synthesis inhibitors, phenidone, BW 755C and nordihydroguaiaretic acid. 4 Plasma SRS-A levels were determined in guinea-pigs following antigen challenge. The appearance of SRS-A in the plasma preceded the onset of bronchoconstriction and SRS-A levels remained elevated throughout its development. Coincident with the inhibition of bronchoconstriction by the SRS-A synthesis inhibitor, phenidone, was a dose-dependent reduction in plasma SRS-A. The intravenous ED50 in each case was 4 mg/kg. 5 This model of antigen-induced SRS-A-mediated bronchoconstriction should prove useful for the in vivo evaluation and development of therapeutics which regulate the synthesis of SRS-A.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001986:Bronchial Spasm / Q000097:blood / Q000276:immunology*; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects; D013189:SRS-A / Q000097:blood / Q000502:physiology*; D013997:Time Factors
D000941:Antigens; D013189:SRS-A; D010047:Ovalbumin; D011738:Pyrilamine