Effect of AA-2414 on early and late bronchial responses in actively sensitized guinea-pigs.
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.
Tohda
Y
Y
Fourth Department of Internal Medicine, School of Medicine, Kinki University, Osaka, Japan.
Muraki
M
M
Kubo
H
H
Iwanaga
T
T
Nakajima
S
S
Fukuoka
M
M
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000494:pharmacology*; D006632:Histamine / Q000008:administration & dosage; D007958:Leukocyte Count; D008163:Luminescent Measurements; D010047:Ovalbumin / Q000008:administration & dosage; D017382:Reactive Oxygen Species; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D016227:Benzoquinones; D006538:Heptanoic Acids; D017382:Reactive Oxygen Species; C060230:seratrodast; D013928:Thromboxane A2; D006632:Histamine; D010047:Ovalbumin