The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling

Tingting Li, Sam R. Holmstrom, Serkan Kir, Michihisa Umetani, Daniel R. Schmidt, Steven A. Kliewer, David J. Mangelsdorf

Research output: Contribution to journalArticlepeer-review

196 Scopus citations


TGR5 is a G protein-coupled bile acid receptor present in brown adipose tissue and intestine, where its agonism increases energy expenditure and lowers blood glucose. Thus, it is an attractive drug target for treating human metabolic disease. However, TGR5 is also highly expressed in gallbladder, where its functions are less well characterized. Here, we demonstrate that TGR5 stimulates the filling of the gallbladder with bile. Gallbladder volume was increased in wild-type but not Tgr5-/- mice by administration of either the naturally occurring TGR5 agonist, lithocholic acid, or the synthetic TGR5 agonist, INT-777. These effects were independent of fibroblast growth factor 15, an enteric hormone previously shown to stimulate gallbladder filling. Ex vivo analyses using gallbladder tissue showed that TGR5 activation increased cAMP concentrations and caused smooth muscle relaxation in a TGR5-dependent manner. These data reveal a novel, gallbladder-intrinsic mechanism for regulating gallbladder contractility. They further suggest that TGR5 agonists should be assessed for effects on human gallbladder as they are developed for treating metabolic disease.

Original languageEnglish (US)
Pages (from-to)1066-1071
Number of pages6
JournalMolecular Endocrinology
Issue number6
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


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