Capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption by blocking TRPV4 channels in healthy and colitic mice

作者全名："Wan, Hanxing; Chen, Xiong Ying; Zhang, Fenglian; Chen, Jun; Chu, Fenglan; Sellers, Zachary M.; Xu, Feng; Dong, Hui"

作者地址："[Wan, Hanxing; Chen, Xiong Ying; Xu, Feng; Dong, Hui] Chongqing Med Univ, Dept Pediat Intens Care Unit, Childrens Hosp, Chongqing, Peoples R China; [Wan, Hanxing; Chen, Xiong Ying; Xu, Feng; Dong, Hui] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Wan, Hanxing; Chen, Xiong Ying; Xu, Feng; Dong, Hui] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Wan, Hanxing; Chen, Xiong Ying; Xu, Feng; Dong, Hui] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Zhang, Fenglian; Chen, Jun; Chu, Fenglan; Dong, Hui] Army Med Univ, Xinqiao Hosp, Dept Gastroenterol, Chongqing, Peoples R China; [Sellers, Zachary M.] Stanford Univ, Sch Med, Pediat Gastroenterol Hepatol & Nutr, Palo Alto, CA 94304 USA; [Dong, Hui] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA"

通信作者："Xu, F; Dong, H (通讯作者)，Chongqing Med Univ, Dept Pediat Intens Care Unit, Childrens Hosp, Chongqing, Peoples R China.; Xu, F; Dong, H (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China.; Xu, F; Dong, H (通讯作者)，Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China.; Xu, F; Dong, H (通讯作者)，Chongqing Key Lab Pediat, Chongqing, Peoples R China.; Dong, H (通讯作者)，Army Med Univ, Xinqiao Hosp, Dept Gastroenterol, Chongqing, Peoples R China.; Dong, H (通讯作者)，Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA."

来源：JOURNAL OF BIOLOGICAL CHEMISTRY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000793483000008

JCR分区：Q2

影响因子：4.8

年份：2022

卷号：298

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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 (I-sc) 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 I-sc but significantly inhibited carbachol-and caffeine-induced intestinal I-sc in WT mice. Capsaicin similarly inhibited the intestinal I-sc 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 I-sc via Na+/glucose cotransporter was suppressed by TRPV4 activation, which could be relieved by capsaicin. Capsaicin also stimulated ouabain-and amiloridesensitive colonic I-sc. Finally, we found that dietary capsaicin ameliorated the UC phenotype, suppressed hyperaction of TRPV4 channels, and rescued the reduced ouabain-and amiloride-sensitive I-sc. We therefore conclude that capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption predominantly by blocking TRPV4 channels to exert its benefi & nbsp;cial anti-colitic action."

基金机构："National Natural Science Foundation of China [81972328, 81873544]"

基金资助正文：Funding and additional information-These studies were supported by research grants from the National Natural Science Foundation of China (81972328 to X. H. W and No. 81873544 to H. D) .