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  • Title: Regulation of the synthesis and release of slow-reacting substance of anaphylaxis from sensitized monkey lung.
    Author: Weichman BM, Hostelley LS, Bostick SP, Muccitelli RM, Krell RD, Gleason JG.
    Journal: J Pharmacol Exp Ther; 1982 May; 221(2):295-302. PubMed ID: 6176708.
    Abstract:
    Immunological challenge of sensitized fragmented cynomolgus monkey lung with anti-human IgE (immunoglobulin E) induced the appearance of slow reacting substance of anaphylaxis (SRS-A) in the tissue and evoked the release of SRS-A into the Tyrode's supernatant. The elevation of tissue or residual SRS-A levels was maximal 2 min after anti-IgE challenge and remained at that plateau for at least 60 min. The released SRS-A, first detectable 3 to 5 min after challenge, achieved a plateau by 10 min. Both the released and residual SRS-A were similarly inactivated by soybean lipoxidase and were antagonized by FPL 55712 on the guinea-pig ileum. Isoproterenol, 5, 8, 11, 14-eicosatraynoic acid and SK & F 64398 all inhibited the anti-IgE induced elevation in residual SRS-A and blocked SRS-A release. Indomethacin stimulated both the elevation of residual SRS-A and the amount released. Removal of the Tyrode's supernatant containing 209 +/- 73 U of released SRS-A/g of tissue 20 min after anti-IgE resulted in the release of an additional 239 +/- 69 U/g; residual SRS-A levels remained at the plateau level. Incubation of the Tyrode's supernatant from challenged, but not control, tissue with fresh lung tissue caused a 90 +/- 7% inhibition of SRS-A release from the fresh tissue. Leukotriene D4 at 5 to 50 ng/ml (concentrations relevant to SRS-A release) showed a concentration-dependent inhibition of SRS-A release, but no effect on histamine release. Leukotriene C4 at 5 to 50 ng/mg failed to significantly alter the amount of SRS-A release. However, at 150 ng/ml, significant inhibition was observed which, in part, may have been produced by metabolism to leukotriene D4. These results demonstrate a potential role for LTD in regulating the amount of SRS-A released from monkey lung.
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