Inhibition of antigen-induced airway hyperresponsiveness by a thromboxane A2 receptor antagonist (AA-2414) in Ascaris suum-allergic dogs.
We studied changes in airway responsiveness to acetylcholine (ACh) after antigen inhalation in Ascaris suum (A. suum)-allergic dogs. Airway responsiveness was determined by obtaining a dose-response curve of lung resistance plotted against increasing concentrations of ACh aerosol before and after inhalation of A. suum antigen. To determine the role of thromboxane A2 (TXA2) in the airway response, we tested the effect of a TXA2 receptor antagonist, AA-2414, in A. suum-allergic dogs. The procedure was repeated in each dog at an interval of 2 weeks to evaluate the effect of AA-2414 in a crossover manner. The dogs showing an airway response to antigen showed an increase in airway responsiveness to ACh 2, 4 and 6 h after antigen inhalation. The increase in airway responsiveness was significantly inhibited by administration of AA-2414 (5 mg/kg, i.v.) before antigen inhalation. These results suggest that TXA2 may be involved in antigen-induced airway hyperresponsiveness (AHR) in dogs.
Matsumoto
T
T
Pharmaceutical Research Laboratories II, Takeda Chemical Industries, Ltd. Osaka, Japan.
Ashida
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology*; D017165:Ascaris suum / Q000276:immunology*; D016227:Benzoquinones; D016084:Bronchoconstriction / Q000502:physiology; D004285:Dogs; D005260:Female; D006538:Heptanoic Acids; D006967:Hypersensitivity / Q000276:immunology*; D008297:Male; D011809:Quinones / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology*; D013928:Thromboxane A2 / Q000502:physiology
D000947:Antigens, Helminth; D016227:Benzoquinones; D006538:Heptanoic Acids; D011809:Quinones; D017482:Receptors, Thromboxane; C060230:seratrodast; D013928:Thromboxane A2; D000109:Acetylcholine