Letter | Published:

Enzymatic assembly of slow reacting substance

Naturevolume 287pages5152 (1980) | Download Citation



When basophils or mast cells are stimulated by a specific antigen they release chemical mediators, including a potent broncho-constrictor, slow reacting substance of anaphylaxis (SRS-A). The structure of SRS from a mouse mastocytoma1,2 and rat basophilic leukaemia (RBL-1) cells3 has been identified as a thioether of arachidonic acid and glutathione2,3 [not a thioether of cysteine as was originally thought1]. SRS has been named leukotriene (LT) C and may be formed by a novel lipoxygenase pathway which also synthesizes 5,6-oxido-7,9,ll,14-icosatetraenoic acid (LTA) and 5,12-dihydroxy-6,8,10,14-icosatetraenoic acid (LTB)1,4. Homogenates of RBL-1 cells, when incubated with 14C-arachidonic acid, form 5-hydroxy-icosatetraenoic acid (5-HETE) and 5,12-dihydroxy- and 5,6-dihydroxy-icosatetraenoic acid5. The latter is the spontaneous breakdown product of the labile intermediate LTA4. 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.

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  1. Department of Pharmacology, Washington University Medical School, St Louis, Missouri, 63110

    • B. A. Jakschik
    •  & L. H. Lee


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