Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Docosahexaenoic Acid Selectively Suppresses U46619- and PGF-Induced Contractions in Guinea Pig Tracheal Smooth Muscles
Keisuke Obara Rikako InabaMirai KawakitaMontserrat De Dios RegaderaTomomi UetakeAzusa MurataNanako NishiokaKota KurokiKento YoshiokaYoshio Tanaka
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2022 Volume 45 Issue 2 Pages 240-244

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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 (PGF) 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 (5 × 10−7 M) (vs. control), although it did not suppress the contractions induced by higher concentrations (U46619: 10−7 M; PGF: 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 (10−8–10−5 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 (10−8 M) and PGF (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. Therefore, DHA may be a useful therapeutic agent against asthma associated with tracheal/bronchial hyper-constriction caused by prostanoids including TXA2 and PGF.

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