The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders #
Abstract
TGR5 (Gpbar-1) is a plasma membrane-bound, G protein–coupled receptor for bile acids. TGR5 messenger RNA (mRNA) has been detected in many tissues, including rat cholangiocytes and mouse gallbladder. A role for TGR5 in gallstone formation has been suggested, because TGR5 knockout mice did not develop gallstones when fed a lithogenic diet. In this study, expression and localization of TGR5 was studied in human gallbladders. TGR5 mRNA and protein were detected in all 19 gallbladders. Although TGR5 mRNA was significantly elevated in the presence of gallstones, no such relation was found for TGR5 protein levels. In order to study the localization of TGR5 in human gallbladders, a novel antibody was generated. The receptor was localized in the apical membrane and the rab11-positive recycling endosome of gallbladder epithelial cells. Furthermore, the TGR5 staining colocalized with the cyclic adenosine monophosphate–regulated chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) and the apical sodium-dependent bile salt uptake transporter, suggesting a functional coupling of TGR5 to bile acid uptake and chloride secretion. Stimulation with bile acids significantly increased cyclic adenosine monophosphate concentration in human gallbladder tissue. Incubation of gallbladder epithelial cells with a TGR5 agonist led to a rise of N -(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE)-fluorescence, suggestive of a decrease in intracellular chloride concentration. The TGR5 agonist–dependent increase in MQAE-fluorescence was absent in TGR5 knockout mice or in the presence of a CFTR inhibitor, indicating that TGR5 mediates chloride secretion via activation of CFTR. The presence of the receptor in both the plasma membrane and the recycling endosome indicate that TGR5 can be regulated by translocation. Conclusion: The data suggest a role for TGR5 in bile acid–induced fluid secretion in biliary epithelial cells. (Hepatology 2009.)
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Cited by
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Metadata
- Authors
- Keitel, V., Cupisti, K., Ullmer, C., Knoefel, W. T., Kubitz, R., & Häussinger, D.
- Venue
- Hepatology
- Published
- 2009-09
- Volume
- 50
- Issue
- 3
- Pages
- 861-870
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2028990131
- Cited by
- 290
- References
- 42
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 2191 d)
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