An in vivo model for measuring antigen-induced SRS-A-mediated bronchoconstriction and plasma SRS-A levels in the guinea-pig

Br J Pharmacol. 1983 Jan;78(1):67-74. doi: 10.1111/j.1476-5381.1983.tb09363.x.

Abstract

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.

MeSH terms

  • Animals
  • Antigens / immunology*
  • Bronchial Spasm / blood
  • Bronchial Spasm / immunology*
  • Guinea Pigs
  • Male
  • Ovalbumin / pharmacology
  • Pyrilamine / pharmacology
  • Respiration / drug effects
  • SRS-A / blood
  • SRS-A / physiology*
  • Time Factors

Substances

  • Antigens
  • SRS-A
  • Ovalbumin
  • Pyrilamine