Secondary bile acid lithocholic acid attenuates neurally evoked ion transport in the rat distal colon.

IF 1.3 4区医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedical Research-tokyo Pub Date : 2022-01-01 DOI:10.2220/biomedres.43.223

Kohei Takahashi, Yuko Kuwahara, Ikuo Kato, Shinji Asano, Takaharu Kozakai, Yoshinori Marunaka, Atsukazu Kuwahara

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引用次数: 1

Abstract

The inhibitory action of the secondary bile acid lithocholic acid (LCA) on neurally evoked Cl^-/HCO₃^- secretion was investigated using the Ussing-chambered mucosal-submucosal preparation from the rat distal colon. Electrical field stimulation (EFS) evoked cholinergic and noncholinergic secretory responses in the rat distal colon. The responses were almost completely blocked by TTX (10^-6 M) but not atropine (10^-5 M) or hexamethonium (10^-4 M). The selective antagonist for VIP receptor 1 (VPAC1) greatly reduced the EFS-evoked response. Thus, the rat distal colon may be predominantly innervated by noncholinergic VIP secretomotor neurons. Basolateral addition of 6 × 10^-5 M LCA inhibited the EFS-evoked response. The inhibitory action of LCA was partly rescued by the Y2R antagonist BIIE0246. The bile acid receptor TGR5 agonist INT-777 mimicked the LCA-induced inhibitory action. Immunohistochemical staining showed the colocalization of TGR5 and PYY on L cells. TGR5 immunoreactivity was also found in VIP-immunoreactive submucosal neurons which also expressed the PYY receptor, Y2R. These results suggest that LCA inhibits neurally evoked Cl^-/HCO₃^- secretion through the activation of TGR5 on L cells and cholinergic- and VIP-secretomotor neurons in the submucosal plexus. Furthermore, the inhibitory mechanism may involve TGR5-stimulated PYY release from L cells and Y2R activation in VIP-secretomotor neurons.

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继发性胆汁酸胆酸减弱大鼠远端结肠神经诱导离子转运。

采用大鼠远端结肠粘膜下乌斯室制备方法，研究了继发性胆汁酸石胆酸(LCA)对神经诱导的Cl-/HCO3-分泌的抑制作用。电场刺激可引起大鼠远端结肠胆碱能和非胆碱能分泌反应。TTX (10-6 M)几乎完全阻断了这些反应，但阿托品(10-5 M)和六甲索铵(10-4 M)则没有。VIP受体1的选择性拮抗剂(VPAC1)大大降低了efs诱发的反应。因此，大鼠结肠远端可能主要受非胆碱能VIP分泌运动神经元支配。基底外侧添加6 × 10-5 M LCA可抑制efs诱发的反应。Y2R拮抗剂BIIE0246部分恢复了LCA的抑制作用。胆汁酸受体TGR5激动剂INT-777模拟lca诱导的抑制作用。免疫组化染色显示TGR5和PYY在L细胞上共定位。在vip免疫反应性的粘膜下神经元中也发现了TGR5免疫反应性，这些神经元也表达PYY受体Y2R。这些结果表明，LCA通过激活粘膜下丛L细胞和胆碱能运动神经元和vip分泌运动神经元的TGR5，抑制神经诱导的Cl-/HCO3-分泌。此外，抑制机制可能与tgr5刺激L细胞释放PYY和vip分泌运动神经元激活Y2R有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedical Research-tokyo 医学-医学：研究与实验

CiteScore

2.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..