Effects of modulators of arachidonic acid metabolism on the synthesis and release of slow-reacting substance of anaphylaxis.

1 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. 2 Both monocytes (macrophages) and mast cells appear to be involved in the synthesis and release of SRS-A. 3 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. 4 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. 5 The results suggest that a lipoxygenase is important in the synthesis and release by SRS-A.