2. Academic Validation
  3. 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

  • J Biol Chem. 2022 May;298(5):101847. doi: 10.1016/j.jbc.2022.101847.
Hanxing Wan 1,  Xiong Ying Chen 1,  Fenglian Zhang 2,  Jun Chen 2,  Fenglan Chu 2,  Zachary M Sellers 3,  Feng Xu 4,  Hui Dong 5
Affiliations

Affiliations

  • 1 Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Pediatrics, Chongqing, China.
  • 2 Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 3 Pediatric Gastroenterology Hepatology & Nutrition, Stanford University School of Medicine, Palo Alto, California, USA.
  • 4 Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Pediatrics, Chongqing, China. Electronic address: xufeng9899@163.com.
  • 5 Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Pediatrics, Chongqing, China; Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China; Department of Medicine, School of Medicine, University of California, San Diego, California, USA. Electronic address: h2dong@ucsd.edu.
PMID: 35314195 DOI: 10.1016/j.jbc.2022.101847
Abstract

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.

Keywords

Na(+)/K(+)-ATPase; TRPV4 channels; epithelial Na(+) channels; short-circuit current; ulcerative colitis.

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