Premium
An in vivo model for measuring antigen‐induced SRS‐A‐mediated bronchoconstriction and plasma S RS‐ A levels in the guinea‐pig
Author(s) -
Anderson Wayne H.,
O'Donnell Margaret,
Simko Beverly A.,
Welton Ann F.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb09363.x
Subject(s) - bronchoconstriction , pyrilamine , in vivo , pharmacology , guinea pig , anaphylaxis , ovalbumin , propranolol , antagonist , medicine , chemistry , immunology , antigen , asthma , allergy , biology , receptor , microbiology and biotechnology
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 ED 50 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.