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A G protein-coupled receptor responsive to bile acids
Yuji Kawamata1, Ryo Fujii, Masaki Hosoya
1Discovery Research Laboratories 1, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan.
The Journal of Biological Chemistry
|January 14, 2003
Summary
Scientists discovered TGR5, a novel cell surface receptor for bile acids. This G protein-coupled receptor plays a role in suppressing macrophage functions, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
- Endocrinology
Background:
- Bile acids are known to interact with nuclear receptors.
- A cell surface receptor for bile acids had not been previously identified.
Purpose of the Study:
- To identify and characterize a novel cell surface receptor for bile acids.
- To investigate the role of this receptor in immune cell function.
Main Methods:
- Utilized Chinese hamster ovary cells expressing TGR5 to assess bile acid responsiveness.
- Quantified TGR5 mRNA expression in human and rabbit monocytes/macrophages.
- Investigated the effects of bile acids on macrophage functions, including phagocytosis and cytokine production, in both primary cells and a TGR5-transfected monocytic cell line (THP-1).
Main Results:
- Identified TGR5 as a novel G protein-coupled receptor responsive to bile acids.
- Demonstrated that bile acids activate TGR5, leading to receptor internalization, ERK activation, GTPγS binding, and cAMP production.
- Found abundant TGR5 expression in monocytes/macrophages.
- Showed that bile acids suppress macrophage functions, such as phagocytosis and lipopolysaccharide-stimulated cytokine production, in a TGR5-dependent manner.
Conclusions:
- TGR5 is a functional cell surface receptor for bile acids.
- TGR5 mediates the suppressive effects of bile acids on macrophage functions, suggesting its involvement in immune regulation.