| Autor: |
Obara K; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Inaba R; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Kawakita M; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., De Dios Regadera M; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Uetake T; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Murata A; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Nishioka N; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Kuroki K; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Yoshioka K; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University., Tanaka Y; Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University. |
| Abstrakt: |
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 2 (TXA 2 ) 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 D 4 (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 TXA 2 and PGF 2α . |
