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  • Title: Effect of synthetase inhibitors and receptor antagonists in antigen-induced contraction of human lung parenchyma.
    Author: Fukushima C, Shimoda T, Matsuse H, Matsuo N, Takao A, Obase Y, Kohno S, Asai S.
    Journal: Ann Allergy Asthma Immunol; 1998 Mar; 80(3):245-50. PubMed ID: 9532973.
    Abstract:
    BACKGROUND: Chemical mediators induce bronchoconstriction, enhance vascular permeability, and promote inflammation. The use of synthetase inhibitors and receptor antagonists of these mediators may be useful in the treatment of asthma. OBJECTIVES: We evaluated the role of chemical mediators in mite antigen-induced contraction in resected human lung parenchyma using synthetase inhibitors and receptor antagonists for these mediators. METHODS: Resected human lung parenchymal specimens were passively sensitized with serum obtained from patients with asthma showing an IgE RAST score for mites > or = 5. The specimens were suspended in Magnus bath filled with buffer. After confirmation of contraction using PGF2 alpha, buffer or synthetase inhibitors or receptor antagonists of various chemical mediators were added. Contraction of parenchyma was induced by the addition of mite antigen, and the concentration of thromboxaneB2 (TXB2), leukotriene (LT), and histamine was measured before and after contraction. RESULTS: Thromboxane A2 (TXA2) synthetase inhibitors significantly inhibited TXB2 release but not contraction. Leukotriene synthetase inhibitors significantly inhibited both LT release and contraction. The magnitude of the inhibitory effect was in the order of LT receptor antagonist > 5-lipoxygenase inhibitor > TXA2 receptor antagonist > PAF antagonist, TXA2 synthetase inhibitor, antihistamine > cyclooxygenase inhibitor. CONCLUSION: Among chemical mediators, LT appears to be the most closely involved in the immediate antigen-induced contractile response in resected human lung parenchyma. Receptor antagonists produced a more marked inhibition of antigen-induced contraction than synthetase inhibitors.
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