scholarly journals Deficiency of Both Farnesoid X Receptor and Takeda G Protein–Coupled Receptor 5 Exacerbated Liver Fibrosis in Mice

Hepatology ◽  
2019 ◽  
Vol 70 (3) ◽  
pp. 955-970 ◽  
Author(s):  
Jessica M. Ferrell ◽  
Preeti Pathak ◽  
Shannon Boehme ◽  
Tricia Gilliland ◽  
John Y. L. Chiang
Keyword(s):  
Liver Fibrosis ◽  
G Protein ◽  
Farnesoid X Receptor ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Identification of potential dual agonists of FXR and TGR5 using e-pharmacophore based virtual screening

2015 ◽  
Vol 11 (5) ◽  
pp. 1305-1318 ◽  
Author(s):  
Thangaraj Sindhu ◽  
Pappu Srinivasan
Keyword(s):  
Bile Acid ◽  
Virtual Screening ◽  
Drug Development ◽  
G Protein ◽  
Farnesoid X Receptor ◽  
G Protein Coupled Receptor ◽  
Treatment Of Diabetes ◽  
Bile Acid Receptors ◽  
G Protein Coupled

Farnesoid X receptor and Takeda G-protein-coupled receptor-5 are well known bile acid receptors and act as promising targets for the drug development and treatment of diabetes.

scholarly journals Bile acids and ceramide overcome the entry restriction for GII.3 human norovirus replication in human intestinal enteroids

2020 ◽  
Vol 117 (3) ◽  
pp. 1700-1710 ◽  
Author(s):  
Kosuke Murakami ◽  
Victoria R. Tenge ◽  
Umesh C. Karandikar ◽  
Shih-Ching Lin ◽  
Sasirekha Ramani ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Early Stage ◽  
Age Groups ◽  
Acid Sphingomyelinase ◽  
Farnesoid X Receptor ◽  
Apical Surface ◽  
G Protein Coupled Receptor ◽  
Endosomal Acidification ◽  
G Protein Coupled

Human noroviruses (HuNoVs) cause sporadic and epidemic outbreaks of gastroenteritis in all age groups worldwide. We previously reported that stem cell-derived human intestinal enteroid (HIE) cultures support replication of multiple HuNoV strains and that some strains (e.g., GII.3) replicate only in the presence of bile. Heat- and trypsin-treatment of bile did not reduce GII.3 replication, indicating a nonproteinaceous component in bile functions as an active factor. Here we show that bile acids (BAs) are critical for GII.3 replication and replication correlates with BA hydrophobicity. Using the highly effective BA, glycochenodeoxycholic acid (GCDCA), we show BAs act during the early stage of infection, BA-dependent replication in HIEs is not mediated by detergent effects or classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling but involves another G protein-coupled receptor, sphingosine-1-phosphate receptor 2, and BA treatment of HIEs increases particle uptake. We also demonstrate that GCDCA induces multiple cellular responses that promote GII.3 replication in HIEs, including enhancement of 1) endosomal uptake, 2) endosomal acidification and subsequent activity of endosomal/lysosomal enzyme acid sphingomyelinase (ASM), and 3) ceramide levels on the apical membrane. Inhibitors of endosomal acidification or ASM reduce GII.3 infection and exogenous addition of ceramide alone permits infection. Furthermore, inhibition of lysosomal exocytosis of ASM, which is required for ceramide production at the apical surface, decreases GII.3 infection. Together, our results support a model where GII.3 exploits rapid BA-mediated cellular endolysosomal dynamic changes and cellular ceramide to enter and replicate in jejunal HIEs.

scholarly journals A dual agonist of farnesoid X receptor (FXR) and the G protein–coupled receptor TGR5, INT-767, reverses age-related kidney disease in mice

2017 ◽  
Vol 292 (29) ◽  
pp. 12018-12024 ◽  
Author(s):  
Xiaoxin X. Wang ◽  
Yuhuan Luo ◽  
Dong Wang ◽  
Luciano Adorini ◽  
Mark Pruzanski ◽  
...  
Keyword(s):  
Kidney Disease ◽  
G Protein ◽  
Farnesoid X Receptor ◽  
G Protein Coupled Receptor ◽  
Age Related ◽  
G Protein Coupled ◽  
Dual Agonist

Vanadium compounds cause activation of G protein-coupled receptor signaling

2020 ◽  
Author(s):  
Debbie C. Crans ◽  
Duaa Althumairy ◽  
Heide Murakami ◽  
B. George Barisas ◽  
Deborah Roess
Keyword(s):  
G Protein ◽  
Receptor Signaling ◽  
G Protein Coupled Receptor ◽  
Vanadium Compounds ◽  
G Protein Coupled
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