Introduction of ADRB3

ADRB3 is a beta-adrenergic receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily characterized by seven transmembrane domains of 22-28 amino acids. Structurally, the N-terminus of ADRB3 protein is extracellular and glycosylated. The C-terminus is intracellular and has no sites for phosphorylation by protein kinase A (PKA) and β-adrenoceptor kinase (βARK). TM3, TM4, TM5, and TM6 are essential for ligand binding. TM2 and TM7 are involved in Gs activation. The activation of this receptor produces several signaling pathways, including activation of adenylyl cyclase and cAMP-dependent phosphorylation. ADRB3 is insensitive to the commonly used beta-adrenergic receptor antagonists.

Functions of ADRB3 Membrane Protein

ADRB3 receptors are identified in a variety of tissues and mediate various physiological effects. They inhibit the contractile activity of ileum and colon, induce relaxation of airway smooth muscle, produce peripheral vasodilation, reduce the contractile force in human ventricular muscle, and stimulate L-type calcium current in human atrial myocytes. More importantly, it is discovered to play an important role in energy metabolism through its role in enhancing lipolysis, mobilization of free fatty acids into the circulation in white adipose tissue, and thermogenesis in brown adipose tissue. Polymorphisms of the ADRB3 gene has been reported to be associated with resistance to weight loss. Studies have reported ADRB3 as a potential target for anti-obesity and anti-diabetes therapy.

Fig.1 Intracellular signaling cascade governing ADRB3 stimulated glucose uptake by brown adipocytes. (Hankir, 2016)

Applications of ADRB3 Membrane Protein in Literature

1. Jin J., et al. Design and synthesis of aryloxypropanolamine as β3-adrenergic receptor antagonist in cancer and lipolysis. European Journal of Medicinal Chemistry. 2018, 150: 757-770. PMID:29574204

This article described the design, synthesis, and evaluation of a series of novel L-748,337 derivatives as selective human β3-adrenergic receptor antagonists. The most potent one was found to alleviate weight loss and inhibit tumor growth.

2. Procino G., et al. β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function. Kidney International. 2016, 90(3): 555-567. PMID: 27206969

This article investigated the expression and the possible physiologic role of β3-adrenergic receptor (β3-AR) in mouse kidney. The findings uncover the antidiuretic effect of β3-AR stimulation in the kidney and suggest that β3-AR agonism might be useful to bypass AVPR2-inactivating mutations.

3. Hong S., et al. Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes. Mol Metab. 2018, 12: 25-38. PMID: 29661693

This article demonstrated that ERK activation in adipocytes and subsequent phosphorylation of the β3 adrenergic receptor on Serine 247 are critical regulatory steps in the enhanced adipocyte lipolysis of obesity.

4.Zhang R., et al. Effects of carvedilol on ventricular remodeling and the expression of β3-adrenergic receptor in a diabetic rat model subjected myocardial infarction. International Journal of Cardiology. 2016, 222: 178-184. PMID: 27497092

This article assessed effects of carvedilol on ventricular remodeling and expression of β3-adrenergic receptor (β3-AR) and Gi protein in a rat model of diabetes subjected to myocardial infarction. The results showed that the expression of this receptor and its coupled Gi protein was increased in this model and Carvedilol treatment prevented many of these harmful effects.

5. Cao X., Li Y. β₃-Adrenergic Receptor Regulates Hepatic Apolipoprotein A-I Gene Expression. Journal of Clinical Lipidology. 2017, 11(5): 1168-1176. PMID: 28802864

This article investigated the molecular mechanism of β3-AR-mediated regulation of hepatic apoA-I gene expression. The results showed that β3-AR-mediated upregulation of hepatic apoA-I expression might be attributed to the increased activity of the apoA-I promoter, HNF-4, and HNF-3. Thus, β3-AR might exert an anti-atherosclerotic effect.

ADRB3 Preparation Options

Our technical platform has extensive experience in reconstituting membrane proteins, including GPCRs, ion channels, transporters, into functional and active formats for subsequent structural and functional studies. Available preparation options include detergent micelles, liposomes, nanodiscs, amphipols, and SMALPs. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-ADRB3 antibody development services.

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Reference

1. Hankir M K, et al. (2016). A BAT-centric approach to the treatment of diabetes: turn on the brain. Cell Metabolism. 24(1), 31-40.

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