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 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 hyperconstriction caused by prostanoids including TXA 2 and PGF 2α .

Inhibitory mechanisms of docosahexaenoic acid on carbachol-, angiotensin II-, and bradykinin-induced contractions in guinea pig gastric fundus smooth muscle

“…We have proposed TP receptor antagonism and functional inhibition of VDCCs as the mechanisms by which DHA produces immediate inhibitory activity against SM contractions induced by a TP receptor agonist/prostanoids and non-prostanoid agonists [8][9][10][11]17,18 . In addition, we now show that inhibition of SOCC-mediated Ca 2+ influx is a new mechanism responsible for the DHA-induced inhibition of SM contractions (Supplementary Fig.…”

“…Some of the preventive/beneficial effects of the long-term intake of DHA are generally assumed to be related to the suppression of inflammatory prostanoid production 6 . However, we previously showed that DHA immediately and selectively inhibited the contractions induced by U46619 (a thromboxane A 2 (TXA 2 ) mimetic) and prostaglandin F 2α (PGF 2α ) in vascular and tracheal smooth muscles (SMs) [7][8][9][10][11] . Furthermore, based on the results of studies with human prostanoid TP receptor-expressing cells, we demonstrated that an antagonistic effect against TP receptors is partly responsible for the immediate inhibitory actions exhibited by DHA 10 .…”

Effects of NP-1815-PX, a P2X4 Receptor Antagonist, on Contractions in Guinea Pig Tracheal and Bronchial Smooth Muscles

“…8) Recordings of Isometric Tension Changes Isometric tension changes of TSM/BSM preparations were recorded using the methods described in a previous report. 9) The TSM and BSM preparations were suspended with stainless steel hooks (outer diameter 200 µm) in a 5-mL organ bath (UC-5; UFER Medical Instrument, Kyoto, Japan) filled with Locke-Ringer solution aerated with mixed gas (95% O 2 + 5% CO 2 ) and maintained at 32 ± 1 °C (pH = 7.4). Tension changes were isometrically recorded using force displacement transducers (T7-8-240; Orientec Co., Ltd., Tokyo, Japan), a signal conditioner (MSC-2; Primtech Corp., Tokyo, Japan), PowerLab/4sp (ADInstruments Pty.…”