Enzymatic assembly of slow reacting substance

Abstract

When basophils or mast cells are stimulated by a specific antigen they release chemical mediators, including a potent bronchoconstrictor, slow reacting substance of anaphylaxis (SRS-A). The structure of SRS from a mouse mastocytoma and rat basophilic leukaemia (RBL-1) cells has been identified as a thioether or arachidonic acid and glutathione [not a thioether of cystene as was originally thought]. SRS has been named leukotriene (LT) C and may be formed by a novel lipoxygenase pathway which also synthesizes 5,6-oxido-7,9,11,14-icosatetraenoic acid (LTA) and 5,12-dihydroxy-6,8,10,14-icosatetraenoic acid (LTB). Homogenates of RBL-1 cells, when incubated with C-arachidonic acid, form 5-hydroxy-icosatetraenoic acid (5-HETE) and 5,12-dihydroxy- and 5,6-dihydroxy-icosatetraenoic acid. The latter is the spontaneous breakdown product of the labile intermediate LTA. Formation of both compounds is stimulated by calcium. We have now produced biologically active SRS in a cell-free system generated from RBL-1 cells. Glutathione was essential for SRS synthesis and calcium stimulated its formation.