Effect of Y-24180, a Platelet-Activating Factor-Receptor Antagonist, on the Antigen-Induced Airway Microvascular Leakage in Guinea Pigs

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The inhibitory effect of Y-24180 ((±)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6, 9-dimethyl-6<I>H</I>-thieno[3, 2-<I>f</I>][1, 2, 4]triazolo[4, 3-a][1, 4]diazepine) on platelet-activating factor (PAF)- or antigen-induced airway microvascular leakage was studied in guinea pigs by oral administration. The tissue content of extravasated Evans blue dye was used as an index of plasma exudation in the trachea, main bronchi, central intrapulmonary airways and peripheral intrapulmonary airways. In all of these tissues. Y-24180 potently inhibited the leakage induced by PAF. The ED<SUB>50</SUB> Value of Y-24180 determined in each of the tissues was approximately 0.02 mg/kg, demonstrating that the inhibitory potency of Y-24180 is 4-6 times that of WEB 2086, another PAF antagonist. Even at a dose of 10 mg/kg, however, Y-24180 showed no inhibitory effect on the leakage induced by leukotriene (LT) D<SUB>4</SUB>, histamine or bradykinin. In the antigeninduced model of guinea pigs sensitized with aerosolized ovalbumin, Y-24180 (0.1-10 mg/kg) and WEB 2086 (1-100 mg/kg) potently inhibited the microvascular leakage in all of the examined airway tissues except for the trachea. At 1-100 mg/kg, however, both ON0-1078, an LT-receptor antagonist, and OKY-046, a thromboxane A<SUB>2</SUB> synthetase inhibitor, prevented partially but not significantly the antigen-induced leakage. These results provide evidence that endogenous PAF partially mediates the antigen-induced airway microvascular leakage in guinea pigs.

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  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 72(3), 209-215, 1996-11-01

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008675897
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4080030
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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