Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
Department of Pharmacy, Faculty of Pharmacy, Musashino University.
Biol Pharm Bull. 2021;44(8):1129-1139. doi: 10.1248/bpb.b21-00362.
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are n-3 polyunsaturated fatty acids (PUFAs), and are abundant in fish oil. These n-3 PUFAs have been reported to improve the lower gastrointestinal (LGI) disorders such as ulcerative colitis and Crohn's disease through their anti-inflammatory effects. However, there are few studies on the effect of n-3 PUFAs on motility of the LGI tract, such as the ileum and colon, the parts frequently affected by these inflammatory disorders. To elucidate the effects of DHA and EPA on the LGI tract motility, we performed comparative evaluation of their effects and linoleic acid (LA), an n-6 PUFA, on contractions in the ileal and colonic longitudinal smooth muscles (LSMs) isolated from guinea pigs. In the ileal and colonic LSMs, DHA and EPA (3 × 10 M each) significantly inhibited contractions induced by acetylcholine (ACh), histamine, and prostaglandin (PG) F (vs. control), and these effects are stronger than that of LA (3 × 10 M). In the colonic LSMs, DHA and EPA also significantly inhibited contractions induced by PGD (vs. control). In addition, DHA and EPA significantly inhibited CaCl-induced ileal and colonic LSM contractions in Ca-free 80 mM-KCl solution (vs. control). Any ileal and colonic LSM contractions induced by ACh, histamine, PGF, and CaCl were completely suppressed by verapamil (10 M), a voltage-gated/dependent Ca channel (VGCC/VDCC) inhibitor. These findings suggest that DHA and EPA could improve the abnormal contractile functions of the LGI tract associated with inflammatory diseases, partly through inhibition of VGCC/VDCC-dependent ileal and colonic LSM contractions.
二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）是 n-3 多不饱和脂肪酸（PUFAs），在鱼油中含量丰富。这些 n-3 PUFAs 已被报道通过其抗炎作用改善下胃肠道（LGI）疾病，如溃疡性结肠炎和克罗恩病。然而，关于 n-3 PUFAs 对 LGI 道运动的影响，如经常受这些炎症性疾病影响的回肠和结肠的运动，研究较少。为了阐明 DHA 和 EPA 对 LGI 道运动的影响，我们比较评估了它们对豚鼠回肠和结肠纵向平滑肌（LSMs）收缩的作用，以及亚油酸（LA），一种 n-6 PUFAs。在回肠和结肠 LSMs 中，DHA 和 EPA（各 3×10-5 M）显著抑制乙酰胆碱（ACh）、组胺和前列腺素（PG）F 诱导的收缩（与对照相比），其作用强于 LA（3×10-5 M）。在结肠 LSMs 中，DHA 和 EPA 也显著抑制 PGD 诱导的收缩（与对照相比）。此外，DHA 和 EPA 显著抑制 CaCl2 在无钙 80mM-KCl 溶液中诱导的回肠和结肠 LSM 收缩（与对照相比）。维拉帕米（10μM），一种电压门控/钙通道（VGCC/VDCC）抑制剂，完全抑制 ACh、组胺、PGF 和 CaCl2 诱导的任何回肠和结肠 LSM 收缩。这些发现表明，DHA 和 EPA 可以改善与炎症性疾病相关的 LGI 道异常收缩功能，部分通过抑制 VGCC/VDCC 依赖性回肠和结肠 LSM 收缩。
