Alteration of eicosanoid production in the sensitized guinea pig lung by CS-518

Abstract

The effects of CS-518 (sodium 2-(1-imidazolymetthyl)-4,5-dihydrobenzo [b]thiophene-6-carboxylate), a thromboxane A 2 Antigen challenge enhaned the production of thromboxane A 2 as well as histamine and peptide leukotrienes in lung fragments. Exogenous leukoriene D 4 also stimulated significant thromboxane A 2 production int he non-sensitized lung in vitro. CS-518 was effective in preventing the thromboxane A 2 production induced by either antigen or leukotriene D 4, and the IC 50 values were 90 and 7.5 ng/ml (320 and 27 nM), respectively. CS-518 markedly potentiated the production of prostaglandin E 2 and I 2 with slight inhibition of leukotriene formation, but indomethacin significantly stimulated leukotriene production. When CS-518 was administered orally, it induced long-lasting inhibition of thromboxane A 2 production and potentiation of prostaglandin I 2 production in guinea pig lung. Thus, CS-518 not only inhibited thromboxane production but also improved the change in arachidonic acid metabolism in the guinea pig bronchoalveolar tissue during allergic reaction in vivo as well as in vitro, which suggests amelioration of the asthmatic condition.