The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain
Abstract
TGR5 (Gpbar-1) is a membrane-bound bile acid receptor in the gastrointestinal tract and immune cells with pleiotropic actions. As shown in the present study, TGR5 is also expressed in astrocytes and neurons. Here, TGR5 may act as a neurosteroid receptor, which is activated by nanomolar concentrations of 5β-pregnan-3α-ol-20-one and micromolar concentrations of 5β-pregnan-3α-17α-21-triol-20-one and 5α-pregnan-3α-ol-20-one (allopregnanolone). TGR5 stimulation in astrocytes and neurons is coupled to adenylate cyclase activation, elevation of intracellular Ca(2+) and the generation of reactive oxygen species. In cultured rat astrocytes, TGR5 mRNA is downregulated in the presence of neurosteroids and ammonia already at concentrations of 0.5 mmol L(-1). Furthermore, TGR5 protein levels are significantly reduced in isolated rat astrocytes after incubation with ammonia. A marked downregulation of TGR5 mRNA is also found in cerebral cortex from cirrhotic patients dying with hepatic encephalopathy (HE) when compared with brains from noncirrhotic control subjects. It is concluded that TGR5 is a novel neurosteroid receptor in brain with implications for the pathogenesis of HE.
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TGR5 is expressed in brain and peripheral neurons, glial and microglial cells, and can be activated by several neurosteroids.
“TGR5, expressed in brain and peripheral neurons, as well as glial and microglial cells, can be activated by several neurosteroids (305).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [305]
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References 49 · Cited by 274
- Authors
- Keitel, V., Görg, B., Bidmon, H. J., Zemtsova, I., Spomer, L., Zilles, K., & Häussinger, D.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Forschungszentrum Jülich (DE)
- Corresponding author
- Häussinger, Dieter
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2010-07-21
- Volume
- 58
- Issue
- 15
- Pages
- 1794-1805
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2062301025
- Cited by
- 274
- References
- 49
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 19 · 2023: 19 · 2022: 29 · 2021: 27 · 2020: 27 · 2019: 14 · 2018: 18 · 2017: 11 · 2016: 17 · 2015: 16 · 2014: 11 · 2013: 14 · 2012: 6
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Funders
- F. Hoffmann-La Roche
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- TGR5, bile acid receptors, astrocytes, neurons, allopregnanolone, 5alpha-pregnan-3alpha-ol-20-one, adenylate cyclase activation, intracellular calcium, reactive oxygen species, ammonia, hepatic encephalopathy, liver cirrhosis, cerebral cortex, receptor down-regulation
- MeSH terms
- Cyclic AMP, Animals, Animals, Newborn, Astrocytes, Brain, Calcium, Cells, Cultured, Cholagogues and Choleretics, Dose-Response Relationship, Drug, Colforsin, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Humans, Luminescent Proteins, Microtubule-Associated Proteins, Neurons, RNA, Messenger, Taurolithocholic Acid, Transfection, Rats, Wistar, Reactive Oxygen Species, Neurotransmitter Agents, Statistics, Nonparametric, Coculture Techniques, Receptors, G-Protein-Coupled, CREB-Binding Protein, Rats
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