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000010805 0247_ $$2pmid$$apmid:20665558
000010805 0247_ $$2DOI$$a10.1002/glia.21049
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000010805 082__ $$a610
000010805 084__ $$2WoS$$aNeurosciences
000010805 1001_ $$0P:(DE-HGF)0$$aKeitel, V.$$b0
000010805 245__ $$aThe bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain
000010805 260__ $$aBognor Regis [u.a.]$$bWiley-Liss$$c2010
000010805 300__ $$a1794 - 1805
000010805 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000010805 440_0 $$011101$$aGlia$$v58$$x0894-1491
000010805 500__ $$aGrant sponsor: Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 575 Dusseldorf "Experimental Hepatology.".
000010805 520__ $$aTGR5 (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.
000010805 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems (FUEK409)$$cFUEK409$$x0
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000010805 65320 $$2Author$$ahepatic encephalopathy
000010805 65320 $$2Author$$aastrocyte
000010805 65320 $$2Author$$aammonia
000010805 65320 $$2Author$$aneuron
000010805 65320 $$2Author$$acalcium
000010805 650_2 $$2MeSH$$aAnimals
000010805 650_2 $$2MeSH$$aAnimals, Newborn
000010805 650_2 $$2MeSH$$aAstrocytes: drug effects
000010805 650_2 $$2MeSH$$aAstrocytes: metabolism
000010805 650_2 $$2MeSH$$aBrain: cytology
000010805 650_2 $$2MeSH$$aBrain: metabolism
000010805 650_2 $$2MeSH$$aCREB-Binding Protein: metabolism
000010805 650_2 $$2MeSH$$aCalcium: metabolism
000010805 650_2 $$2MeSH$$aCells, Cultured
000010805 650_2 $$2MeSH$$aCholagogues and Choleretics: pharmacology
000010805 650_2 $$2MeSH$$aCoculture Techniques
000010805 650_2 $$2MeSH$$aCyclic AMP: metabolism
000010805 650_2 $$2MeSH$$aDose-Response Relationship, Drug
000010805 650_2 $$2MeSH$$aForskolin: pharmacology
000010805 650_2 $$2MeSH$$aGene Expression Regulation: drug effects
000010805 650_2 $$2MeSH$$aGene Expression Regulation: physiology
000010805 650_2 $$2MeSH$$aGlial Fibrillary Acidic Protein: metabolism
000010805 650_2 $$2MeSH$$aHumans
000010805 650_2 $$2MeSH$$aLuminescent Proteins
000010805 650_2 $$2MeSH$$aMicrotubule-Associated Proteins: metabolism
000010805 650_2 $$2MeSH$$aNeurons: drug effects
000010805 650_2 $$2MeSH$$aNeurons: metabolism
000010805 650_2 $$2MeSH$$aNeurotransmitter Agents: pharmacology
000010805 650_2 $$2MeSH$$aRNA, Messenger: metabolism
000010805 650_2 $$2MeSH$$aRats
000010805 650_2 $$2MeSH$$aRats, Wistar
000010805 650_2 $$2MeSH$$aReactive Oxygen Species: metabolism
000010805 650_2 $$2MeSH$$aReceptors, G-Protein-Coupled: antagonists & inhibitors
000010805 650_2 $$2MeSH$$aReceptors, G-Protein-Coupled: genetics
000010805 650_2 $$2MeSH$$aReceptors, G-Protein-Coupled: physiology
000010805 650_2 $$2MeSH$$aStatistics, Nonparametric
000010805 650_2 $$2MeSH$$aTaurolithocholic Acid: pharmacology
000010805 650_2 $$2MeSH$$aTransfection: methods
000010805 650_7 $$00$$2NLM Chemicals$$aCholagogues and Choleretics
000010805 650_7 $$00$$2NLM Chemicals$$aCrebbp protein, rat
000010805 650_7 $$00$$2NLM Chemicals$$aGlial Fibrillary Acidic Protein
000010805 650_7 $$00$$2NLM Chemicals$$aGpbar1 protein, rat
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000010805 650_7 $$00$$2NLM Chemicals$$aReactive Oxygen Species
000010805 650_7 $$00$$2NLM Chemicals$$aReceptors, G-Protein-Coupled
000010805 650_7 $$0516-90-5$$2NLM Chemicals$$aTaurolithocholic Acid
000010805 650_7 $$060-92-4$$2NLM Chemicals$$aCyclic AMP
000010805 650_7 $$066428-89-5$$2NLM Chemicals$$aForskolin
000010805 650_7 $$07440-70-2$$2NLM Chemicals$$aCalcium
000010805 650_7 $$0EC 2.3.1.48$$2NLM Chemicals$$aCREB-Binding Protein
000010805 650_7 $$2WoSType$$aJ
000010805 7001_ $$0P:(DE-HGF)0$$aGörg, B.$$b1
000010805 7001_ $$0P:(DE-HGF)0$$aBidmon, H.J.$$b2
000010805 7001_ $$0P:(DE-HGF)0$$aZemtsova, I.$$b3
000010805 7001_ $$0P:(DE-HGF)0$$aSporner, L.$$b4
000010805 7001_ $$0P:(DE-Juel1)131714$$aZilles, K.$$b5$$uFZJ
000010805 7001_ $$0P:(DE-Juel1)VDB9577$$aHäussinger, D.$$b6$$uFZJ
000010805 773__ $$0PERI:(DE-600)1474828-9$$a10.1002/glia.21049$$gVol. 58, p. 1794 - 1805$$p1794 - 1805$$q58<1794 - 1805$$tGlia$$v58$$x0894-1491$$y2010
000010805 8567_ $$uhttp://dx.doi.org/10.1002/glia.21049
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