Inhibitory action of OKY-046 HCI, a specific TXA2 synthetase inhibitor, on platelet activating factor (PAF)-induced airway hyperresponsiveness of guinea pigs: Role of TXA2 in development of PAF-induced nonspecific airway hyperresponsiveness

• TAKEHANA Yasuo

  Central Research Laboratories, Kissei Pharmaceutical Cc., Ltd.

• HAMANO Shuichiro

  Central Research Laboratories, Kissei Pharmaceutical Cc., Ltd.

• KIKUCHI Shinji

  Central Research Laboratories, Kissei Pharmaceutical Cc., Ltd.

• KOMATSU Hidetada

  Central Research Laboratories, Kissei Pharmaceutical Cc., Ltd.

• OKEGAWA Tadao

  Minase Research Institute, Ono Pharmaceutical Co., Ltd.

• IKEDA Shigeru

  Central Research Laboratories, Kissei Pharmaceutical Cc., Ltd.

書誌事項

タイトル別名

• Inhibitory action of OKY-046HCl, a specific TXA2 synthetase inhibitor, on platelet activating factor(PAF)-induced airway hyperresponsiveness of guinea pigs: Role of TXA2 in development of PAF-induced nonspecific airway hyperresponsiveness.

抄録

We studied a role of TXA₂ in the development of PAF-induced nonspecific airway hyperresponsiveness in guinea pigs using a TXA₂ synthetase inhibitor (OKY-046·HCI) and a stable TXA₂ mimetic agent (STA₂). Inhalation of PAF (1 μg/ml) and STA₂ (1 or 10 ng/ml) increased the airway response to acetylcholine (ACh), histamine, leukotriene D₄ and electrical vagal stimulation. Intraduodenal administration (i.d.) of OKY-046·HCI (100 mg/kg) inhibited PAF-induced airway hyperresponsiveness. However, OKY-046·HCI (30 mg/kg, i.v.) did not suppress STA₂-induced airway hyperresponsiveness. Neither hexamethonium (1 mg/ kg, i.v.) nor hemicholinium-3(10 mg/kg, i.v.) prevented the increase in the airway response to ACh after inhalation of PAF and STA₂. In the presence of atropine (0.5 mg/kg, i.p.), PAF-induced airway hyperresponsiveness to histamine did not change. OKY-046·HCI (100 mg/kg, i.d.) inhibited the increase in ACh (10^-8 M)-induced ⁴⁵Ca uptake into the lung tissue from PAF-inhalated guinea pigs. Inhalation of STA₂ increased the number (B_max) of muscarinic and H₁-histaminergic receptors in the lung tissue from guinea pigs, but no changes were found on β-adrenoceptors. These results suggest that TXA₂ should act on the smooth muscle cells or alter functions of muscarinic and H₁-histaminergic receptors, except β-adrenoceptors, and then increase the membrane permeability to extracellular Ca²⁺. We also assume that OKY-046·HCI can inhibit PAF-induced nonspecific airway hyperresponsiveness by suppressing the generation of TXA₂.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 52 (4), 621-630, 1990

  公益社団法人 日本薬理学会

キーワード

• Pharmacology

詳細情報

• CRID: 1390001204286206336
• NII論文ID: 130000832788
• DOI: 10.1254/jjp.52.621
• COI: 1:CAS:528:DyaK3cXitlehtrw%3D
• ISSN: 13473506
• ISSN: 00215198
• PubMed: 2160552
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可