Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice
- Author:
Chen LU
1
;
Hongli LU
;
Xu HUANG
;
Shaohua LIU
;
Jingyu ZANG
;
Yujia LI
;
Jie CHEN
;
Wenxie XU
Author Information
- Publication Type:Original Article
- Keywords: Anoctamin-1; Colitis; Interstitial cells of Cajal; Nitric oxide synthase; Down-regulation
- MeSH: Animals; Blotting, Western; Chloride Channels; Colitis; Colon; Dextrans; Down-Regulation; In Vitro Techniques; Interstitial Cells of Cajal; Mice; Muscle, Smooth; Myoelectric Complex, Migrating; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Polymerase Chain Reaction; RNA, Messenger; Sodium
- From:Journal of Neurogastroenterology and Motility 2019;25(2):316-331
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice. METHODS: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study. RESULTS: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice. CONCLUSION: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.
