Nedocromil sodium inhibits antigen-induced contraction of human lung parenchymal and bronchial strips, and the release of sulphidopeptide-leukotriene and histamine from human lung fragments.
1. The effects of nedocromil sodium on antigen-induced release of sulphidopeptide-leukotrienes and histamine from passively sensitized fragments of human lung, and on antigen-induced contraction of sensitized strips of human lung parenchyma and bronchus, have been studied. 2. Nedocromil sodium 0.1 and 1 microM inhibited leukotriene release from fragments of human lung by 30% and 38% respectively, and histamine release by 43% for both concentrations, but 10 microM was ineffective. The lung fragments, which were passively sensitized to house dust mite, Dermataphagoides pteronyssinus, in control experiments released leukotrienes (6.58 +/- 0.12 nmol equiv. leukotriene C4 per g, n = 6) and histamine (10.3 +/- 1.8 of total tissue histamine, n = 5) when challenged with house dust mite extract. 3. Isolated strips of human lung parenchyma, passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 40% of the maximal histamine response for each strip. Nedocromil sodium 0.1 and 1 microM inhibited these contractions by 50% and 70% of the control response, but 10 microM had no inhibitory effect. 4. Isolated rings from human bronchus, also passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 86% of the maximal histamine response. Nedocromil sodium 1 microM, but not 0.1 or 10 microM, inhibited contractions by 48% of the control response. 5. The therapeutic effects of nedocromil sodium in allergic asthma may depend, partly, on its inhibition of antigen-induced release of leukotrienes and histamine in human lung and its consequent inhibition of antigen-induced contractions of parenchymal and bronchial tissue.
Department of Pharmacology, University of Sydney, Australia.
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008925:Mites / Q000276:immunology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D017835:Nedocromil; D015363:Quinolones / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D002867:Chromones; D015289:Leukotrienes; D015363:Quinolones; D013189:SRS-A; D017835:Nedocromil; C006312:FPL 55712