GPBAR1 - G-Protein Coupled Bile Acid Receptor 1 | Elisa - Clia - Antibody - Protein

GPBA Receptor (GPBAR1)

The GPBA receptor, also known as GPBAR1 or TGR5 (Takeda G protein-coupled bile acid receptor 1), is a G protein-coupled receptor (GPCR) primarily expressed in the liver, gallbladder, intestines, and other tissues. It serves as a key regulator of bile acid signaling and plays diverse roles in metabolic regulation, energy homeostasis, and inflammatory responses.

Structure of GPBAR1

GPBAR1 shares the characteristic seven-transmembrane domain structure typical of GPCRs. It consists of an extracellular N-terminus and an intracellular C-terminus, which interact with intracellular signaling molecules upon ligand binding. GPBAR1 activation leads to downstream signaling events mediated by heterotrimeric G proteins.

Ligands

The primary endogenous ligands for GPBAR1 are bile acids, which are amphipathic molecules synthesized from cholesterol and secreted into the bile by hepatocytes. Bile acids serve multiple physiological functions, including facilitating fat digestion and absorption, regulating cholesterol metabolism, and acting as signaling molecules through interactions with GPBAR1 and other receptors.

Physiological Functions

GPBAR1 signaling exerts diverse effects on various tissues and organ systems:

• Bile Acid Homeostasis: GPBAR1 activation regulates bile acid synthesis, secretion, and transport, contributing to bile acid homeostasis and enterohepatic circulation.
• Metabolic Regulation: GPBAR1 signaling influences glucose metabolism, insulin sensitivity, lipid metabolism, and energy expenditure, suggesting potential roles in metabolic disorders such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease.
• Inflammatory Responses: GPBAR1 activation modulates inflammatory signaling pathways, immune cell function, and cytokine production, implicating its involvement in inflammatory and autoimmune diseases.
• Gastrointestinal Function: GPBAR1 regulates gastrointestinal motility, secretion, and barrier function, influencing processes such as digestion, absorption, and gut microbiota composition.

Clinical Implications

Dysregulation of GPBAR1 signaling is associated with various pathological conditions:

• Metabolic Disorders: Altered GPBAR1 signaling has been implicated in metabolic diseases such as obesity, insulin resistance, dyslipidemia, and fatty liver disease.
• Inflammatory Diseases: GPBAR1 dysfunction may contribute to inflammatory bowel disease (IBD), liver inflammation, and other inflammatory conditions.
• Gastrointestinal Disorders: GPBAR1 activation or inhibition may have therapeutic potential in gastrointestinal disorders such as cholestatic liver diseases, bile acid malabsorption, and functional gastrointestinal disorders.

Therapeutic Potential

Given its roles in metabolic regulation, inflammatory responses, and gastrointestinal function, GPBAR1 represents a promising target for therapeutic intervention. Pharmacological modulation of GPBAR1 activity, either through agonists or antagonists, holds potential for the treatment of metabolic disorders, inflammatory diseases, and gastrointestinal disorders.