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The G Protein‐coupled bile acid receptor, TGR5, is expressed on colonic epithelial cells and regulates ion transport
Author(s) -
Ward Joseph Bernard Jude,
Mróz Magdalena Slawa,
Keely Stephen J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1162.10
Subject(s) - g protein coupled bile acid receptor , carbachol , bile acid , deoxycholic acid , secretion , biology , ion transporter , chemistry , intestinal epithelium , microbiology and biotechnology , receptor , epithelium , endocrinology , biochemistry , membrane , genetics
TGR5 has been implicated in the regulation of intestinal motility and has also been identified as a regulator of Cl − secretion across gallbladder epithelium. However, there is a paucity of information regarding the role of TGR5 in colonic epithelial cells (CECs). Here we sought to investigate a potential role for TGR5 in regulation of CEC ion transport. 6α‐ethyl‐23(S)‐methylcholic acid (INT‐777) was used to activate TGR5. Ion transport was measured by short‐circuit current (I sc ) across muscle‐stripped segments of rat colon. mRNA expression was measured by RT‐PCR. TGR5 localisation was measured by confocal microscopy. TGR5 mRNA and protein were highly expressed in CECs. TGR5 was localised bilaterally in rat colonic crypts. INT‐777 addition to rat colonic mucosa caused a rapid and transient decrease in I sc . This decrease was dependent on the presence of Cl − in the bathing solution. INT‐777 was effective from the basolateral side only. Furthermore, treatment with INT‐777 reduced subsequent Clsecretory responses to carbachol. These studies reveal a novel role for TGR5 in regulating colonic epithelial ion transport. TGR5 activation rapidly reduces basal I sc and inhibits subsequent Cl − secretory responses. Our data suggest that TGR5 may provide a new target for development of drugs to treat intestinal transport disorders. INT‐777 was supplied by Intercept Pharmaceuticals. Funded by Science Foundation Ireland.