SRSA-mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo

Abstract

Antigen challenge of actively sensitized guinea pigs results in the release of histamine, eicosanoids (products of the cyclooxygenase pathway of arachidonic acid metabolism) and slow reacting substance of anaphylaxis (SRS-A). By antagonizing the effects of histamine, serotonin, and acetylcholine, inhibiting the cyclooxygenase pathway and supplying arachidonic acid as substrate, the contribution of SRS-A to anaphylactic bronchospasm can be enhanced, thus allowing suitable quantitation of antagonists. This SRS-A mediated bronchospasm can be inhibited in a dose dependent fashion by FPL55712, a selective antagonist of SRS-A. This system represents an in vivo method capable of detecting compounds which inhibit SRS-A synthesis/release or SRS-A action at the effector organ.