Effect of AA-2414 on early and late bronchial responses in actively sensitized guinea-pigs

J Int Med Res. 2001 May-Jun;29(3):229-35. doi: 10.1177/147323000102900311.

Abstract

The effect of a new thromboxane A2 receptor antagonist, AA-2414, (+/-)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid, on dual bronchoconstriction and airway hyper-reactivity in actively sensitized guinea-pigs was investigated. Immediate and late bronchial responses were seen 1-10 min and 4-7 h, respectively, after inhalation of antigen. In guinea-pigs pretreated with AA-2414, 5 mg/kg orally, the immediate bronchial response was inhibited. An administration of AA-2414 inhibited the late bronchial response. The numbers of eosinophils, neutrophils and macrophages, but not of lymphocytes, in bronchoalveolar lavage fluid were increased at 4 h after antigen inhalation. AA-2414 did not affect the numbers of total cells, eosinophils, neutrophils or macrophages. Sensitized guinea-pigs showed a significant airway hyperreactivity to inhaled histamine, which was not influenced by an administration of AA-2414. Luminol-dependent chemiluminescence of airway-infiltrated cells from sensitized guinea-pigs stimulated with A23187 was slightly inhibited by AA-2414. These results show that AA-2414 inhibits the late asthmatic response and the production of oxygen radicals from airway-infiltrated cells.

MeSH terms

  • Animals
  • Benzoquinones / pharmacology*
  • Bronchi / drug effects*
  • Bronchoalveolar Lavage Fluid / cytology
  • Guinea Pigs
  • Heptanoic Acids / pharmacology*
  • Histamine / administration & dosage
  • Leukocyte Count
  • Luminescent Measurements
  • Ovalbumin / administration & dosage
  • Reactive Oxygen Species
  • Thromboxane A2 / antagonists & inhibitors*

Substances

  • Benzoquinones
  • Heptanoic Acids
  • Reactive Oxygen Species
  • seratrodast
  • Thromboxane A2
  • Histamine
  • Ovalbumin