Docosahexaenoic Acid and Eicosapentaenoic Acid Inhibit the Contractile Responses of the Guinea Pig Lower Gastrointestinal Tract
Docosahexaenoic Acid and Eicosapentaenoic Acid Inhibit the Contractile Responses of the Guinea Pig Lower Gastrointestinal Tract
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DOI：
10.1248/bpb.b21-00362
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发表时间：
2021-08-01
影响因子：
2
通讯作者：
Tanaka, Yoshio
中科院分区：
文献类型：
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作者：
Obara, Keisuke;Kawaguchi, Ayana;Tanaka, Yoshio
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（PUFA），在鱼油中含量丰富。据报道，这些n-3 PUFA可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，很少有关于n-3 PUFA对LGI道（例如回肠和结肠，经常受这些炎性疾病影响的部分）的运动性的影响的研究。为了阐明DHA和EPA对LGI道运动的影响，我们进行了比较评估，其效果和亚油酸（LA），一种n-6 PUFA，对豚鼠回肠和结肠纵向平滑肌（LSMs）的收缩。在回肠和结肠LSM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-2 α诱导的收缩（与对照组相比），这些作用强于LA（3 × 10 - 5 M）。在结肠LSM中，DHA和EPA也显著抑制PGD诱导的收缩（2）（与对照组相比）。此外，DHA和EPA在无Ca 2+的80 mM-KCl溶液中显著抑制Ca 2+诱导的回肠和结肠LSM收缩（与对照组相比）。任何由ACh、组胺、PGF（2 α）和CaCl 2诱导的回肠和结肠LSM收缩均被维拉帕米（10（-5）M）完全抑制，维拉帕米是一种电压门控/依赖性Ca 2+通道（VGCC/VDCC）抑制剂。这些发现表明，DHA和EPA可以改善与炎性疾病相关的LGI道的异常收缩功能，部分地通过抑制VGCC/VDCC依赖性回肠和结肠LSM收缩。
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 x 10(-5) M each) significantly inhibited contractions induced by acetylcholine (ACh), histamine, and prostaglandin (PG) F-2 alpha (vs. control), and these effects are stronger than that of LA (3 x 10(-5) M). In the colonic LSMs, DHA and EPA also significantly inhibited contractions induced by PGD(2) (vs. control). In addition, DHA and EPA significantly inhibited CaCl2-induced ileal and colonic LSM contractions in Ca2+-free 80 mM-KCl solution (vs. control). Any ileal and colonic LSM contractions induced by ACh, histamine, PGF(2 alpha), and CaCl2 were completely suppressed by verapamil (10(-5) M), a voltage-gated/dependent Ca2+ 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.