INVITRO REVERSAL OF ANAPHYLAXIS IN GUINEA-PIG LUNG STRIP BY COMPOUND FPL-55712, AN SRS-A RECEPTOR ANTAGONIST

Lung parenchymal strips obtained from ovalbumin-(OA) sensitized guinea pigs relaxed to small doses of histamine (< 10-7 M) and contracted to antigen (Schultz-Dale response) and high doses of histamine (> 10-7 M). Mepyramine (a specific H1-receptor antagonist) produced reversal of pre-existing maximal contractions to histamine but only weakly reversed contractions to antigen. Compound FPL 55712, a highly selective SRS-A receptor antagonist, produced dose-related reversal of the pre-existing contractions to OA. Indomethacin relaxed lung strips and enhanced contractions to OA. In high doses, mepyramine 5 × 10-5) and FPL 55712 (10-5 to 5 × 10-5) significantly inhibitied in vitro anaphylaxis in guinea pig lung strip. This investigation provides convicing pharmacological evidence that SRS-A plays a major role in in vitro anaphylaxis in the guinea pig lung. © 1979 Springer-Verlag.