TY  - JOUR
AU  - Keitel, V.
AU  - Görg, B.
AU  - Bidmon, H.J.
AU  - Zemtsova, I.
AU  - Sporner, L.
AU  - Zilles, K.
AU  - Häussinger, D.
TI  - The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain
JO  - Glia
VL  - 58
SN  - 0894-1491
CY  - Bognor Regis [u.a.]
PB  - Wiley-Liss
M1  - PreJuSER-10805
SP  - 1794 - 1805
PY  - 2010
N1  - Grant sponsor: Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 575 Dusseldorf "Experimental Hepatology.".
AB  - 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.
KW  - Animals
KW  - Animals, Newborn
KW  - Astrocytes: drug effects
KW  - Astrocytes: metabolism
KW  - Brain: cytology
KW  - Brain: metabolism
KW  - CREB-Binding Protein: metabolism
KW  - Calcium: metabolism
KW  - Cells, Cultured
KW  - Cholagogues and Choleretics: pharmacology
KW  - Coculture Techniques
KW  - Cyclic AMP: metabolism
KW  - Dose-Response Relationship, Drug
KW  - Forskolin: pharmacology
KW  - Gene Expression Regulation: drug effects
KW  - Gene Expression Regulation: physiology
KW  - Glial Fibrillary Acidic Protein: metabolism
KW  - Humans
KW  - Luminescent Proteins
KW  - Microtubule-Associated Proteins: metabolism
KW  - Neurons: drug effects
KW  - Neurons: metabolism
KW  - Neurotransmitter Agents: pharmacology
KW  - RNA, Messenger: metabolism
KW  - Rats
KW  - Rats, Wistar
KW  - Reactive Oxygen Species: metabolism
KW  - Receptors, G-Protein-Coupled: antagonists & inhibitors
KW  - Receptors, G-Protein-Coupled: genetics
KW  - Receptors, G-Protein-Coupled: physiology
KW  - Statistics, Nonparametric
KW  - Taurolithocholic Acid: pharmacology
KW  - Transfection: methods
KW  - Cholagogues and Choleretics (NLM Chemicals)
KW  - Crebbp protein, rat (NLM Chemicals)
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - Gpbar1 protein, rat (NLM Chemicals)
KW  - Luminescent Proteins (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - Mtap2 protein, rat (NLM Chemicals)
KW  - Neurotransmitter Agents (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Receptors, G-Protein-Coupled (NLM Chemicals)
KW  - Taurolithocholic Acid (NLM Chemicals)
KW  - Cyclic AMP (NLM Chemicals)
KW  - Forskolin (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
KW  - CREB-Binding Protein (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:20665558
UR  - <Go to ISI:>//WOS:000284060900003
DO  - DOI:10.1002/glia.21049
UR  - https://juser.fz-juelich.de/record/10805
ER  -