OKY-046 inhibits anaphylactic bronchoconstriction and reduces histamine level in bronchoalveolar lavage fluid in sensitized guinea pigs

• Published in: Prostaglandins Vol. 39; no. 6; p. 623
• Main Authors: Nambu, F, Murakata, S, Shiraji, T, Omawari, N, Sawada, M, Okegawa, T, Kawasaki, A, Ikeda, S
• Format: Journal Article
• Language: English
• Published: United States 01-06-1990
• Subjects: 6-Ketoprostaglandin F1 alpha - metabolism; Acrylates - pharmacology; Anaphylaxis; Animals; Bordetella pertussis - immunology; Cyclooxygenase Inhibitors; Guinea Pigs; Histamine Release - drug effects; Immunization; Indomethacin - pharmacology; Male; Methacrylates - pharmacology; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - physiology; Pulmonary Alveoli - physiopathology; Pyrilamine - pharmacology; Thromboxane B2 - metabolism
• ISSN: 0090-6980
• DOI: 10.1016/0090-6980(90)90023-O

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.