Docosahexaenoic Acid Selectively Suppresses U46619- and PGF_2α-Induced Contractions in Guinea Pig Tracheal Smooth Muscles

Abstract

We investigated the potential inhibitory effects of docosahexaenoic acid (DHA) on the contractions of guinea pig tracheal smooth muscles in response to U46619 (a thromboxane A₂ (TXA₂) mimetic) and prostaglandin F_2α (PGF_2α) to examine whether this n-3 polyunsaturated fatty acid suppresses prostanoid-induced tracheal contractions. DHA (3 × 10⁻⁵ M) significantly suppressed tracheal contractions elicited by lower concentrations of U46619 (10⁻⁸ M) and PGF_2α (5 × 10⁻⁷ M) (vs. control), although it did not suppress the contractions induced by higher concentrations (U46619: 10⁻⁷ M; PGF_2α: 10⁻⁵ M). Supporting these findings, DHA (4 × 10⁻⁵ M/6 × 10⁻⁵ M) shifted the concentration-response curves for U46619 (10⁻⁹–10⁻⁶ M) and PGF_2α (10⁻⁸–10⁻⁵ M) to the right. However, the slope of the regression line in the Schild plot of DHA vs. U46619/PGF_2α was larger than unity. The tracheal contractions induced by U46619 (10⁻⁸ M) and PGF_2α (5 × 10⁻⁷ M) were significantly suppressed by the prostanoid TP receptor antagonist SQ 29,548 (10⁻⁶ M) (vs. ethanol-treated). In contrast, DHA (4 × 10⁻⁵ M) did not show significant inhibitory effects on the contractions induced by acetylcholine (10⁻⁸–10⁻⁴ M), histamine (10⁻⁸–10⁻⁴ M), and leukotriene D₄ (10⁻¹¹–10⁻⁷ M) (vs. ethanol-treated). These findings indicate that DHA selectively suppresses tracheal contractions induced by U46619 and PGF_2α. Therefore, DHA may be a useful therapeutic agent against asthma associated with tracheal/bronchial hyper-constriction caused by prostanoids including TXA₂ and PGF_2α.