ANAPHYLAXIS IN CHOPPED GUINEA PIG LUNG II. ENHANCEMENT 0]~ THE ANAPHYLACTIC RELEASE OF I-IIsTAMINE AND SLOW REACTING SUBSTANCE BY CERTAIN DIBASIC ALIPHATIC ACIDS AND IN~III$1TION BY MONOBASIC FATTY AcIDs

Although several workers have produced in vitro inhibition of the anaphylactic reaction with metabolic inhibitors (1, 2) and we have observed inhibition with chymotrypsin substrates and inhibitors (3), enhancement of the in vitro anaphylactic reaction has not been previously reported. While evaluating c-amino caproic acid, an inhibitor of plasminogen activation (4, 5), for its effect on the anaphylactic reaction in chopped guinea pig lung, we found that caproic acid (hexanoic) was a more potent inhibitor than ~-amino caproic acid. I t was further observed that the ability of the unsubstituted fatty acids to inhibit the anaphylactic release of histamine increased with increasing chain length from valeric to dodecanoic acid. Substitution of the fatty acid with an alpha amino group completely abolished the inhibitory potential. This led to a study of other structurally related compounds, and the discovery that the four carbon dibasic aliphatic acids, succinic and maleic (c/s-butenedioic), greatly enhance the anaphylactic release of histamine and slow reacting substance SRS-A. Other four carbon dibasic acids, such as malic and fumaric (trans-butenedioic), and several dibasic acids of greater or lesser chain length were without effect. The inhibition produced by the monobasic fatty acids can be reversed by the enhancing effect of succinic acid and vice versa. Thus, these data show that compounds normally present in mammalian tissue can greatly influence the intensity of the in vitro anaphylactic reaction in chopped guinea pig lung.