Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct

World J Gastroenterol. 2023 Oct 14;29(38):5374-5382. doi: 10.3748/wjg.v29.i38.5374.

Abstract

Background: Many studies have shown that interstitial Cajal-like cell (ICLC) abnormalities are closely related to a variety of dynamic gastrointestinal disorders. ICLCs are pacemaker cells for gastrointestinal movement and are involved in the transmission of nerve impulses.

Aim: To elucidate the expression profile and significance of cholecystokinin-A (CCK-A) receptors in ICLCs in the common bile duct (CBD), as well as the role of CCK in regulating CBD motility through CCK-A receptors on CBD ICLCs.

Methods: The levels of tyrosine kinase receptor (c-kit) and CCK-A receptors in CBD tissues and isolated CBD cells were quantified using the double immunofluorescence labeling technique. The CCK-mediated enhancement of the movement of CBD muscle strips through CBD ICLCs was observed by a muscle strip contraction test.

Results: Immunofluorescence showed co-expression of c-kit and CCK-A receptors in the CBD muscularis layer. Observations of isolated CBD cells showed that c-kit was expressed on the surface of ICLCs, the cell body and synapse were colored and polygonal, and some cells presented protrusions and formed networks adjacent to the CBD while others formed filaments at the synaptic terminals of local cells. CCK-A receptors were also expressed on CBD ICLCs. At concentrations ranging from 10-6 mol/L to 10-10 mol/L, CCK promoted CBD smooth muscle contractility in a dose-dependent manner. In contrast, after ICLC removal, the contractility mediated by CCK in CBD smooth muscle decreased.

Conclusion: CCK-A receptors are highly expressed on CBD ICLCs, and CCK may regulate CBD motility through the CCK-A receptors on ICLCs.

Keywords: Cholecystokinin-A receptors; Common bile duct; Interstitial Cajal-like cells; Tyrosine kinase receptor.

MeSH terms

  • Animals
  • Cholecystokinin / metabolism
  • Common Bile Duct
  • Gallbladder*
  • Guinea Pigs
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Cholecystokinin A / metabolism
  • Telocytes* / metabolism

Substances

  • Receptor, Cholecystokinin A
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases
  • Cholecystokinin