EFFECTS OF MODULATORS OF ARACHIDONIC-ACID METABOLISM ON THE SYNTHESIS AND RELEASE OF SLOW-REACTING SUBSTANCE OF ANAPHYLAXIS

Slow‐reacting substance of anaphylaxis (SRS‐A) was released in the peritoneum of passively sensitized rats challenged with ovalbumin and from rat isolated peritoneal cells stimulated with calcium ionophore A23187. Both monocytes (macrophages) and mast cells appear to be involved in the synthesis and release of SRS‐A. The immunological release of SRS‐A in vivo is enhanced by indomethacin and inhibited by dexamethasone, mepacrine, 1‐phenyl‐3‐pyrazolidone (1‐P‐3‐P), and methylimidazole. SRS‐A release induced by A23187 in vitro is inhibited by dexamethasone, indomethacin, 1‐P‐3‐P, eicosatetraynoic acid (ETA) and 15‐hydroperoxy arachidonic acid. The inhibition induced by dexamethasone, indomethacin and 1‐P‐3‐P is reduced by an increase in the calcium concentration from 1 mm to 5 mm, whereas the inhibition induced by ETA is increased. The results suggest that a lipoxygenase is important in the synthesis and release by SRS‐A. 1979 British Pharmacological Society