J Neurogastroenterol Motil.  2019 Apr;25(2):316-331. 10.5056/jnm18173.

Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice

• Lu C
• Lu H
• Huang X
• Liu S
• Zang J
• Li Y
• Chen J
• Xu W

• KMID: 2449103
• DOI: http://doi.org/10.5056/jnm18173

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.

Keyword

Anoctamin-1; Colitis; Interstitial cells of Cajal; Nitric oxide synthase; Down-regulation

MeSH Terms

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*
Chloride Channels
Dextrans
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
RNA, Messenger
Sodium