Journal Article

PreJuSER-10805

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain

Keitel, V. ; Görg, B. ; Bidmon, H. J. ; Zemtsova, I. ; Sporner, L. ; Zilles, K.FZJ* ; Häussinger, D.FZJ*

2010
Wiley-Liss Bognor Regis [u.a.]

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Please use a persistent id in citations: doi:10.1002/glia.21049

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.

Keyword(s): Animals (MeSH) ; Animals, Newborn (MeSH) ; Astrocytes: drug effects (MeSH) ; Astrocytes: metabolism (MeSH) ; Brain: cytology (MeSH) ; Brain: metabolism (MeSH) ; CREB-Binding Protein: metabolism (MeSH) ; Calcium: metabolism (MeSH) ; Cells, Cultured (MeSH) ; Cholagogues and Choleretics: pharmacology (MeSH) ; Coculture Techniques (MeSH) ; Cyclic AMP: metabolism (MeSH) ; Dose-Response Relationship, Drug (MeSH) ; Forskolin: pharmacology (MeSH) ; Gene Expression Regulation: drug effects (MeSH) ; Gene Expression Regulation: physiology (MeSH) ; Glial Fibrillary Acidic Protein: metabolism (MeSH) ; Humans (MeSH) ; Luminescent Proteins (MeSH) ; Microtubule-Associated Proteins: metabolism (MeSH) ; Neurons: drug effects (MeSH) ; Neurons: metabolism (MeSH) ; Neurotransmitter Agents: pharmacology (MeSH) ; RNA, Messenger: metabolism (MeSH) ; Rats (MeSH) ; Rats, Wistar (MeSH) ; Reactive Oxygen Species: metabolism (MeSH) ; Receptors, G-Protein-Coupled: antagonists & inhibitors (MeSH) ; Receptors, G-Protein-Coupled: genetics (MeSH) ; Receptors, G-Protein-Coupled: physiology (MeSH) ; Statistics, Nonparametric (MeSH) ; Taurolithocholic Acid: pharmacology (MeSH) ; Transfection: methods (MeSH) ; Cholagogues and Choleretics ; Crebbp protein, rat ; Glial Fibrillary Acidic Protein ; Gpbar1 protein, rat ; Luminescent Proteins ; Microtubule-Associated Proteins ; Mtap2 protein, rat ; Neurotransmitter Agents ; RNA, Messenger ; Reactive Oxygen Species ; Receptors, G-Protein-Coupled ; Taurolithocholic Acid ; Cyclic AMP ; Forskolin ; Calcium ; CREB-Binding Protein ; J ; hepatic encephalopathy (auto) ; astrocyte (auto) ; ammonia (auto) ; neuron (auto) ; calcium (auto)

Note: Grant sponsor: Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 575 Dusseldorf "Experimental Hepatology.".

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Contributing Institute(s):

1. Molekulare Organisation des Gehirns (INM-2)
2. Jülich-Aachen Research Alliance - Translational Brain Medicine (JARA-BRAIN)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (FUEK409) (FUEK409)
2. 89571 - Connectivity and Activity (POF2-89571) (POF2-89571)

Appears in the scientific report 2010

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