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

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