Bile Acid GPCR Assays
Background of Bile Acid Receptors
It has been indicated that bile acids can agitate the G protein-coupled receptors in a second independent signaling pathway, which are essential for endocrine functions, dyslipidemia, liver and hepatic diseases, metabolism, and related disorders. Bile acids, including primary bile acids, cholic and chenodeoxycholic acids, deoxycholic and lithocholic acids, and secondary bile acids, are generated in the liver from cholesterol and stored in the gall bladder. They are acidic sterols, which are the main components of bile, playing a role in absorbing dietary lipids and lipid-soluble vitamins. They also act as signaling molecules that modulate the transcription of genes expressing enzymes and transport proteins, maintaining the homeostasis of bile acids and cholesterol.
Fig.1. Simplified schematic diagram of the regulation of insulin secretion from pancreatic β-cells by metabolites and hormones acting through GPCRs. (Blad, 2012)
Distribution and Function of Bile Acid Receptors
Bile acid receptors (GPBA receptors) are G protein-coupled receptors that are agitated by bile acids. GPBA receptors are principally distributed in the liver, gallbladder, gastrointestinal tract, leukocytes, skeletal muscle, brown adipose, central nervous system, and other organs. The activation of the GPBA receptors increases the energy consumption in brown adipose and skeletal muscle. GPBA receptor activation also affects glucose metabolism and inhibits the production of pro-inflammatory cytokines.
Subtypes and Mechanisms of Bile Acid Receptors
The bile acid receptor family only has one subtype of receptor, the GPBA receptor. It couples GS protein, which stimulates the adenylyl cyclase.
| Receptor | Gene | Mechanism | Agonists |
| GPBA receptors | GPBAR1 |
|
|
Assay List of Bile Acid Receptor
Creative Biolabs can provide a range of assays of bile acid receptor. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Reversal of Endothelial Dysfunction by GPBAR1 Agonism in Portal Hypertension Involves a AKT/FOXOA1 Dependent Regulation of H2S Generation and Endothelin-1 |
| Journal | PloS one |
| Published | 2015 |
| Abstract | GPBAR1 is expressed restricted to sinusoidal and Kuppfer cells in the liver. They used two rodent models, including a cirrhosis rodent model induced by carbon tetrachloride and a liver endothelial dysfunction model induced by methionine feeding. Both models of mice were administered BAR501, 15 mg/kg/day. They also used human liver cells to find out the cystathione-γ-liase (CSE) expression and activity. The study has demonstrated that BAR501 is a potent and selective agonist of GPBAR1, which is a semisynthetic bile acid derivative. |
| Result |
Transactivation assay was used to demonstrate the agonistic selectivity of BAR501 on GPBAR1. BAR501 effectively reduced hepatic perfusion pressure and counteracted the vasoconstriction activity of norepinephrine, and effectively protected against the development of endothelial dysfunction by increasing liver CSE expression and activity and by reducing endothelin (ET)-1 gene expression. BAR501 rescues endothelial dysfunction in rodent models of portal hypertension by exerting genomic and non-genomic effects on CSE, eNOS, and ET-1 in liver sinusoidal cells.
|
Fig.2. GPBAR1 activation by BAR501 modulates the expression/activity of regulated CSE in human LSEC. (Renga, 2015)
References
- Blad, C.; et al. G protein-coupled receptors for energy metabolites as new therapeutic targets. Nature reviews Drug discovery. 2012, 11(8): 603-619.
- Renga, B.; et al. Reversal of endothelial dysfunction by GPBAR1 agonism in portal hypertension involves a AKT/FOXOA1 dependent regulation of H2S generation and endothelin-1. PloS one. 2015, 10(11): e0141082.
