Capsaicin inhibits intestinal Cl(-) secretion and promotes Na(+) absorption by blocking TRPV4 channels in healthy and colitic mice.
Capsaicin inhibits intestinal Cl(-) secretion and promotes Na(+) absorption by blocking TRPV4 channels in healthy and colitic mice.
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辣椒素通过阻断健康小鼠和结肠炎小鼠的 TRPV4 通道来抑制肠道 Cl- 分泌并促进 Na 吸收
DOI：
10.1016/j.jbc.2022.101847
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发表时间：
2022-05
影响因子：
4.8
通讯作者：
Dong, Hui
中科院分区：
文献类型：
--
作者：
Wan, Hanxing;Chen, Xiong Ying;Zhang, Fenglian;Chen, Jun;Chu, Fenglan;Sellers, Zachary M.;Xu, Feng;Dong, Hui
辣椒素作为感觉神经元瞬时受体电位香草酸离子通道亚型1(TRPV1)通道的激活剂已被广泛研究，但对其在胃肠道健康和疾病中的非TRPV1作用知之甚少。在此，我们旨在研究辣椒素作为食物添加剂和药物对溃疡性结肠炎(UC)小鼠肠道离子转运体的药理作用。在Ussing小室中测量WT、TRPV1-和TRPV4-KO小鼠的肠道短路电流(ISC)，并对小肠上皮细胞进行钙成像。我们还对葡聚糖硫酸钠诱导UC后的肠上皮细胞和肠组织进行了免疫印迹、免疫组织化学和免疫荧光检测。我们发现辣椒素不影响WT小鼠基础肠道ISC，但显著抑制卡巴胆碱和咖啡因诱导的肠道ISC。辣椒素对TRPV1 KO小鼠的肠道ISC有类似的抑制作用，但对TRPV4 KO小鼠没有这种抑制作用。我们还确定，胆碱能信号介导的肠道阴离子分泌需要通过TRPV4的钙内流，而辣椒素抑制了这一过程。此外，葡萄糖诱导的空肠Iscvia Na+/葡萄糖共转运体可被TRPV4激活所抑制，辣椒素可减轻这一作用。辣椒素也刺激哇巴因和阿米洛利敏感的结肠ISC。最后，我们发现膳食辣椒素改善了UC的表型，抑制了TRPV4通道的过度反应，并挽救了对哇巴因和阿米洛利敏感的ISC。因此，我们认为辣椒素主要通过阻断TRPV4通道发挥其有益的抗结肠作用，从而抑制肠道氯离子的分泌，促进Na+的吸收。
Although capsaicin has been studied extensively as an activator of the transient receptor potential vanilloid cation channel subtype 1 (TRPV1) channels in sensory neurons, little is known about its TRPV1-independent actions in gastrointestinal health and disease. Here, we aimed to investigate the pharmacological actions of capsaicin as a food additive and medication on intestinal ion transporters in mouse models of ulcerative colitis (UC). The short-circuit current (Isc) of the intestine from WT, TRPV1-, and TRPV4-KO mice were measured in Ussing chambers, and Ca2+ imaging was performed on small intestinal epithelial cells. We also performed Western blots, immunohistochemistry, and immunofluorescence on intestinal epithelial cells and on intestinal tissues following UC induction with dextran sodium sulfate. We found that capsaicin did not affect basal intestinal Isc but significantly inhibited carbachol- and caffeine-induced intestinal Isc in WT mice. Capsaicin similarly inhibited the intestinal Isc in TRPV1 KO mice, but this inhibition was absent in TRPV4 KO mice. We also determined that Ca2+ influx via TRPV4 was required for cholinergic signaling–mediated intestinal anion secretion, which was inhibited by capsaicin. Moreover, the glucose-induced jejunal Iscvia Na+/glucose cotransporter was suppressed by TRPV4 activation, which could be relieved by capsaicin. Capsaicin also stimulated ouabain- and amiloride-sensitive colonic Isc. Finally, we found that dietary capsaicin ameliorated the UC phenotype, suppressed hyperaction of TRPV4 channels, and rescued the reduced ouabain- and amiloride-sensitive Isc. We therefore conclude that capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption predominantly by blocking TRPV4 channels to exert its beneficial anti-colitic action.
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影响因子：
7.7
作者：
Harraz OF;Longden TA;Hill-Eubanks D;Nelson MT
通讯作者：
Nelson MT
影响因子：
64.8
作者：
Gao X;Zhang D;Xu C;Li H;Caron KM;Frenette PS
通讯作者：
Frenette PS
影响因子：
29.4
作者：
HOLZER, P;PABST, MA;LIPPE, IT
通讯作者：
LIPPE, IT
影响因子：
168.9
作者：
BRAEGGER, CP;NICHOLLS, S;MACDONALD, TT
通讯作者：
MACDONALD, TT
DOI：
10.1152/ajpgi.00114.2007
发表时间：
2007-10-01
影响因子：
4.5
作者：
Eijkelkamp, Niels;Kavelaars, Annemieke;Heijnen, Cobi J.
通讯作者：
Heijnen, Cobi J.