TRPV4/NCX1 coupling regulates Ca²⁺-dependent cholecystokinin secretion from enteroendocrine cells to involve the pathogenesis of irritable bowel syndrome-diarrhea in male mice.
- 1Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, China.
- 2Department of Pediatrics, Guangyuan Central Hospital, Guangyuan, Sichuan, China.
Abstract
Although stress can stimulate the vagus nerve via the brain-gut axis to induce enterohormone secretion from enteroendocrine cells (EECs), little is currently known about the roles of ion channels in the regulation of enterohormone secretion and the development of irritable bowel syndrome (IBS). We aimed to investigate whether transient receptor potential vanilloid 4 (TRPV4) channels and Na⁺/Ca²⁺ exchanger 1 (NCX1) are critical for enterohormone secretion and whether they are involved in IBS. Ca²⁺imaging and patch-clamp were applied to STC-1. IBS-diarrhea (IBS-D) mouse model was established by wrap restraint stress (WRS). Western blot verified TRPV4 and NCX1 expressions in STC-1; co-immunoprecipitation demonstrated their physical interaction, and Ca²⁺ imaging and patch-clamp confirmed function and interaction. Carbachol (CCh), a stable analog of acetylcholine (ACh), induced Ca²⁺ signaling and currents in EECs via a functional coupling of TRPV4 and NCX1. Moreover, intestinal cholecystokinin (CCK) transcripts in IBS-D mice were significantly increased, and ACh enhanced intestinal CCK secretion in mice, all of which could be abolished by blockers of TRPV4, NCX1, and CCK receptors. Finally, these blockers alleviated the severity of IBS-D in mice. We reveal a novel TRPV4/NCX1/Ca²⁺/CCK pathway in EECs, which is involved in the pathogenesis of IBS-D. Targeting this pathway may hold promise for the prevention/treatment of IBS-D.
Related
- Carbonic anhydrase VIII regulates IP3R1-dependent Ca ²⁺ signaling to coordinate insulin secretion and hepatic glucose production
- The Central Melanocortin System Regulates Growth Hormone Secretion
- IL27RA ubiquitination by CBL E3 ligase regulates IL27 dependent immune response against EBV- induced infectious mononucleosis
- Novel variant and enteroendocrine hormone deficiency in a patient with proline and glutamate‐rich protein with a coiled coil domain 1 (PERCC1) associated enteropathy: New diagnostic and therapeutic insights
- Eosinophils in autoimmune diseases: context-dependent pathogenesis, functional heterogeneity, and therapeutic translation
BibTeX
@article{wang2026trpv4ncx1,
title = {{TRPV4/NCX1 coupling regulates Ca²⁺-dependent cholecystokinin secretion from enteroendocrine cells to involve the pathogenesis of irritable bowel syndrome-diarrhea in male mice.}},
author = {Jianxin Wang and Xiongying Chen and Shuo Tong and Chengxin Qu and Wei Lu and Hui Dong},
journal = {Physiological reports},
year = {2026},
month = oct,
doi = {10.14814/phy2.71149},
url = {https://europepmc.org/article/MED/42897987},
note = {CC BY},
}
RIS
TY - JOUR
TI - TRPV4/NCX1 coupling regulates Ca²⁺-dependent cholecystokinin secretion from enteroendocrine cells to involve the pathogenesis of irritable bowel syndrome-diarrhea in male mice.
AU - Jianxin Wang
AU - Xiongying Chen
AU - Shuo Tong
AU - Chengxin Qu
AU - Wei Lu
AU - Hui Dong
PY - 2026
DA - 2026/10/01
JO - Physiological reports
DO - 10.14814/phy2.71149
UR - https://europepmc.org/article/MED/42897987
AB - Although stress can stimulate the vagus nerve via the brain-gut axis to induce enterohormone secretion from enteroendocrine cells (EECs), little is currently known about the roles of ion channels in the regulation of enterohormone secretion and the development of irritable bowel syndrome (IBS). We aimed to investigate whether transient receptor potential vanilloid 4 (TRPV4) channels and Na⁺/Ca²⁺ exchanger 1 (NCX1) are critical for enterohormone secretion and whether they are involved in IBS. Ca²⁺imaging and patch-clamp were applied to STC-1. IBS-diarrhea (IBS-D) mouse model was established by wrap restraint stress (WRS). Western blot verified TRPV4 and NCX1 expressions in STC-1; co-immunoprecipitation demonstrated their physical interaction, and Ca²⁺ imaging and patch-clamp confirmed function and interaction. Carbachol (CCh), a stable analog of acetylcholine (ACh), induced Ca²⁺ signaling and currents in EECs via a functional coupling of TRPV4 and NCX1. Moreover, intestinal cholecystokinin (CCK) transcripts in IBS-D mice were significantly increased, and ACh enhanced intestinal CCK secretion in mice, all of which could be abolished by blockers of TRPV4, NCX1, and CCK receptors. Finally, these blockers alleviated the severity of IBS-D in mice. We reveal a novel TRPV4/NCX1/Ca²⁺/CCK pathway in EECs, which is involved in the pathogenesis of IBS-D. Targeting this pathway may hold promise for the prevention/treatment of IBS-D.
SN - 2051-817X
ER -