The investigators further demonstrated that the bile acid receptor TGR5
mediates the effects of elevated bile acids and OCA in the nucleus accumbens, a brain region that plays a central role in reward circuitry.
88 - THE ROLE OF THE TGR5
RECEPTORS AND DEIODINASE II IN 3,4-METHYLENE-DIOXYMETHAMPHETAMINE (MDMA, MOLLY)-INDUCED HYPERTHERMIA.
Also, genetic mutations of TGR5
, a G-protein-coupled receptor that functions as a cell surface receptor for BAs and regulates basal and cholinergic-induced secretion in the colon and colonic transit, can predispose to BAM .
Increased levels of circulating bile acids induced by chronic high-fat feeding upregulate neuronal nitric oxide synthase (nNOS) and bile acid receptor 1 (TGR5
) expression in the gastric myenteric plexus, resulting in enhanced noncholinergic relaxation and delayed gastric emptying .
Bile acids modulate innate and adaptive immunity and are involved in many metabolic and inflammatory processes mainly through activation of the nuclear receptor farnesoid X receptor (FXR), the membrane receptor TGR5
, extra-cellular signal-regulated kinase (ERK), and MAP kinases signalling pathways .
Dietary supplementation with the bile acid cholic acid in mice reverses HFD-induced weight gain by activating D2 and converting T4 to T3 through TGR5
Bile acids play their roles through specific receptors, including nuclear receptors [farnesoid X receptor (FXR), vitamin D receptor (VDR), and pregnane X receptor (PXR)] as well as membrane receptors [G-protein-coupled bile acid receptor 5 (TGR5
), sphingosine-1-phosphate receptor 2 (S1PR2), and muscarinic receptor 2] [11-18], and may activate multiple signaling pathways [protein kinase B (AKT), extracellular regulated protein kinases (ERK1/2), and c-Jun N-terminal kinase (JNK)] [19-22].
The company's GI portfolio includes tenapanor for the treatment of people with irritable bowel syndrome with constipation (IBS-C), and RDX8940, a TGR5
Katsuma S, Hirasawa A, Tsujimoto G (2005) Bile acids promote glucagon-like peptide-1 secretion through TGR5
in a murine enteroendocrine cell line STC-1.
Strehle et al., "Anti-hyperglycemic activity of a TGR5
agonist isolated from Olea europaea," Biochemical and Biophysical Research Communications, vol.
Mu et al., "Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 (TGR5
) is a potential biomarker for hepatitis B virus associated hepatocellular carcinoma," International Journal of Medical Sciences, vol.