OKY-046 inhibits anaphylactic bronchoconstriction and reduces histamine level in bronchoalveolar lavage fluid in sensitized guinea pigs.
We investigated the effects of OKY-046, a potent and selective thromboxane A2 (TxA2) synthetase inhibitor, on anaphylactic bronchoconstriction and release of chemical mediators into airway lumen in sensitized guinea pigs in vivo. OKY-046 dose-dependently inhibited antigen-induced anaphylactic bronchoconstriction with or without mepyramine, a histamine H1 antagonist. In the presence of mepyramine, OKY-046 (300 mg/kg, p.o.) elicited significant reductions in histamine (1 min) and TxB2 increases (1-15 min) in bronchoalveolar lavage (BAL) fluid but significantly increased the plasma level of 6-keto-PGF1 alpha, a stable PGI2 metabolite, after antigen challenge. On the contrary, indomethacin only significantly reduced increases in TxB2 levels. These results suggest that the antiasthmatic effect of OKY-046 is probably due to inhibition of TxA2 synthesis and suppression of histamine release via a PGI2 shunting mechanism.
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
F
F
Nambu
S
S
Murakata
T
T
Shiraji
N
N
Omawari
M
M
Sawada
T
T
Okegawa
A
A
Kawasaki
S
S
Ikeda
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000179:Acrylates / Q000494:pharmacology*; D000707:Anaphylaxis; D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D011738:Pyrilamine / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D000179:Acrylates; D016861:Cyclooxygenase Inhibitors; D008689:Methacrylates; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011738:Pyrilamine; C034364:ozagrel; D007213:Indomethacin