Journal of Gastroenterology

, Volume 54, Issue 11, pp 994–1006 | Cite as

Cystic fibrosis transmembrane conductance regulator modulates enteric cholinergic activities and is abnormally expressed in the enteric ganglia of patients with slow transit constipation

  • Ka Ming Yeh
  • Olle Johansson
  • Huy Le
  • Karan Rao
  • Irit Markus
  • Dayashan Shevy Perera
  • David Zachary Lubowski
  • Denis Warwick King
  • Li Zhang
  • Hongzhuan Chen
  • Lu LiuEmail author
Original Article—Alimentary Tract



Cystic fibrosis transmembrane conductance regulator (CFTR) was recently found in the enteric nervous system, where its role is unclear. We aimed to identify which enteric neuronal structures express CFTR, whether CFTR modulates enteric neurotransmission and if altered CFTR expression is associated with slow transit constipation (STC).


Immunofluorescence double labeling was performed to localize CFTR with various neuronal and glial cell markers in the human colon. The immunoreactivity (IR) of CFTR and choline acetyltransferase (ChAT) on myenteric plexus of control and STC colon was quantitatively analyzed. In control colonic muscle strips, electrical field stimulation (EFS) evoked contractile responses and the release of acetylcholine (ACh) was measured in the presence of the CFTR channel inhibitor, CFTR(inh)-172.


CFTR-IR was densely localized to myenteric ganglia, where it was co-localized with neuronal markers HuC/D and β-tubulin, and glial marker S-100 but little with glial fibrillary acidic protein. Vesicular ACh transport was almost exclusively co-localized with CFTR, but neurons expressing nitric oxide synthase were CFTR negative. Significant reductions of CFTR-IR (P < 0.01) and ChAT-IR (P < 0.05) were observed on myenteric ganglia of STC compared to control. Pre-treatment of colonic muscle strips with CFTR(inh)-172 (10 µM) significantly inhibited EFS-evoked contractile responses (P < 0.01) and ACh release (P < 0.05).


Co-localization of CFTR-IR with cholinergic markers, inhibition of EFS-induced colonic muscle contractility and ACh release by CFTR(inh)-172 suggest that CFTR modulates enteric cholinergic neurotransmission. The downregulation of CFTR and ChAT in myenteric ganglia of STC correlated with the impaired contractile responses to EFS.


CFTR Motility disorder Slow transit constipation 



This study was supported by a project Grant from the National Health and Medical Research Council of Australia (APP1048885), and by the UNSW and Shanghai Jiao Tong University Collaborative Seed Grant. We would like to offer our special thanks to Stelina Drimousis and Erica Diezmos in specimen collection and preparation.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest.

Supplementary material

535_2019_1610_MOESM1_ESM.docx (4.7 mb)
Supplementary file1 (DOCX 4784 kb)
535_2019_1610_MOESM2_ESM.docx (157 kb)
Supplementary file2 (DOCX 157 kb)


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Copyright information

© Japanese Society of Gastroenterology 2019

Authors and Affiliations

  • Ka Ming Yeh
    • 1
  • Olle Johansson
    • 2
  • Huy Le
    • 1
  • Karan Rao
    • 1
  • Irit Markus
    • 1
  • Dayashan Shevy Perera
    • 3
  • David Zachary Lubowski
    • 3
  • Denis Warwick King
    • 3
  • Li Zhang
    • 4
  • Hongzhuan Chen
    • 5
  • Lu Liu
    • 1
    Email author
  1. 1.Department of Pharmacology, Faculty of Medicine, School of Medical SciencesUniversity of New South WalesSydneyAustralia
  2. 2.Faculty of Medicine and Health SciencesLinköping UniversityLinköpingSweden
  3. 3.Sydney Colorectal AssociatesSydneyAustralia
  4. 4.School of Biotechnology and Biomolecular SciencesUniversity of New South WalesSydneyAustralia
  5. 5.School of MedicineShanghai Jiao Tong UniversityShanghaiChina

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