Pharmacological modulation of antigen-induced airway hyperresponsiveness by thromboxane A2 inhibitors in guinea pigs.
The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) and ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperreactivity in guinea pigs were investigated. Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (macrophages, neutrophils, eosinophils and lymphocytes) and the quantity of mediators (thromboxane B2, leukotriene D4 and histamine) in bronchoalveolar lavage fluid increased. All examined drugs inhibited the antigen-induced airway hyperreactivity to acetylcholine. Whereas ketotifen inhibited an accumulation of inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 had no effect on the accumulation of inflammatory cells. OKY-046, but not ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation. These results suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 inhibitors, without affecting the accumulation of inflammatory cells in bronchoalveolar lavage fluid.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Tsuji
F
F
Goto
S
S
Koda
A
A
D000109:Acetylcholine; D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D006168:Guinea Pigs; D007665:Ketotifen / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects / Q000473:pathology
D008689:Methacrylates; D013928:Thromboxane A2; C049855:ONO 3708; D013930:Thromboxane-A Synthase; C034364:ozagrel; D000109:Acetylcholine; D007665:Ketotifen