ArticleDigestive diseases and sciences2018
Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome Is Associated with Upregulation of TMEM16A in Myenteric Plexus.
Article in Digestive diseases and sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Pleiotropic Effects of the NSAID Fenamates on Chloride Channels: Opportunity for Ion Channelopathies?Pharmacology research & perspectives · 2025Review
- Therapeutic effects of Poncirus fructus on colonic dysfunction and visceral pain in a zymosan-induced irritable bowel syndrome mouse model through interstitial cells of Cajal and ion channel modulation.Frontiers in pharmacology · 2025Article
- The effects ofPeerJ · 2022Article
- Intestinal epithelial barrier and neuromuscular compartment in health and disease.World journal of gastroenterology · 2020Review
- The Effects of Short-Chain Fatty Acids on Rat Colonic Hypermotility Induced by Water Avoidance Stress.Drug design, development and therapy · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIrritable bowel syndrome (IBS) is a common disease with intestinal dysmotility, whose mechanism remains elusive. TMEM16A is a calcium-activated chloride channel (CaCC) involved in intestinal slow-wave generation.
aimsTo investigate whether TMEM16A is involved in colonic dysmotility in IBS.
methodsA rat model of IBS was established by chronic water avoidance stress (WAS). Colonic pathological alterations were evaluated histologically, and intestinal motility was assessed by intestinal transit time (ITT) and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response (VMR) to colorectal distension (CRD). TMEM16A expression was evaluated by RT-PCR, Western blot, and immunofluorescence. Colonic muscle strip contractility was measured by isometric transducers, and the effect of niflumic acid (NFA), a CaCC antagonist, on colonic motility was examined.
resultsAfter 10 days of WAS exposure, ITT was decreased and FWC was elevated. Furthermore, VMR magnitude of WAS rats in response to CRD was significantly enhanced. Protein and mRNA levels of TMEM16A in colon were considerably increased after WAS. The percentage of TMEM16A-positive neurons in myenteric plexus (MP) of WAS rats was significantly higher than controls. Pharmacological blockade of TMEM16A activity by NFA considerably enhanced ITT, with concentration-dependent declines in FWC and VMR magnitude in NFA-treated rats. Further, spontaneous contraction of colonic strips of NFA-treated rats was significantly ameliorated in a concentration-dependent manner in vitro.
conclusionsUpregulation of TMEM16A in MP neurons may play an important role in chronic stress-induced colonic hypermotility, making CaCC-blocking drugs a putatively effective treatment method for colonic hypermotility in IBS.
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