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

Abstract

We investigated the effects of OKY-046, a potent and selective thromboxane A 2 (TxA 2 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 H 1 antagonist. In the presence of mepyramine, OKY-046 (300mg/kg, p.o.) elicited significant reductions in histamine (1min) and TxB 2 increases (1–15min) in bronchoalveolar lavage (BAL) fluid but significantly increased the plasma level of 6-keto-PGF 1α, a stable PGI 2 metabolite, after antigen challenge. On the contrary, indomethacin only significantly reduced increases in TxB 2 levels. These results suggest that the antiasthmatic effect of OKY-046 is probably due to inhibition of TxA 2 synthesis and suppression of histamine release via a PGI 2 shunting mechanism.