Apelin Receptor GPCR Assays
Background of Apelin Receptors
The apelin receptor (APJ receptor) is a monomeric transmembrane G protein-coupled receptor, which is homologous to angiotensin receptor I (AT1). Endogenous ligands of APJ receptors include apelin-36, apelin-13, [Pyr1]-apelin-13, and elabela (ELA).
Fig.1. Apelin-associated signaling pathways. (Hu, 2021)
Distribution and Function of Apelin Receptors
APJ receptors are distributed in endothelial cells, cardiomyocytes, lung, brain, heart, spinal cord, spleen, and placenta. Apelin and APJ receptors participate in many physiological and pathological functions, including regulating cardiovascular function, fluid homeostasis, adipocyte endocrine secretion, gastrointestinal and immunomodulatory functions, cell proliferation, apoptosis, and inflammation. Apelin also plays a role in the inhibition of insulin secretion, which is associated with the pathogenesis of diabetes. Besides, overexpression of apelin provokes specific cancers related to endothelial cell migration, proliferation, and neoangiogenesis. Hypotension and protection against HIV cell entrance may be induced by the activation of APJ receptors.
Subtypes and Mechanisms of Apelin Receptors
APL receptor is the only type of apelin receptor family, coupling Gαi and Gαq proteins for signal transduction.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| APL receptor | APLNR |
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Assay List of Apelin Receptor
Creative Biolabs can provide a range of assays of apelin receptor. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Functional Agonists of the Apelin (APJ) Receptor |
| Journal | Probe Reports from the NIH Molecular Libraries Program |
| Published | 2013 |
| Abstract | The apalin receptor system has emerged as a key mediator of cardiovascular homeostasis and mediates multiple pathogenic mechanisms, including hypertension, heart failure, atherosclerosis, and other cardiovascular diseases. This study identified ML221, a potent triglyceride-based selective small molecule APJ functional antagonist. This article describes the synthetic methodology of ML221, the development of structure-activity relationships (SAR), and initial in vitro pharmacologic characterization, including the Parallel Artificial Membrane Permeability Assay (PAMPA), plasma protein binding assay, and microsomal stability assay. |
| Result |
β-arrestin assay technology allows for a direct measure of GPCR activation by detection of β-arrestin binding to the APJ. β-arrestin is fused to an N-terminal deletion mutant of β-galactosidase, while the APL receptor is fused to a complementing fragment. In cells that stably express these fusion proteins, ligands, such as ML221, lead to the interaction of β-arrestin and APL receptor, which results in the formation of a functional enzyme that converts substrate to detectable luminescent signal. ML221 was not detected in the plasma protein binding assay, which indicated ML221 is likely rapidly metabolized in plasma. The result of PAMPA indicated moderate permeability of ML221 that increased with pH. ML221 shows very poor stability in human plasma.
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Fig.2. Dose response curve for ML221 in the APL antagonist assay. (Maloney, 2013)
References
- Hu, G.; et al. The role of apelin/apelin receptor in energy metabolism and water homeostasis: a comprehensive narrative review. Frontiers in Physiology. 2021, 104.
- Maloney, P. R.; et al. Functional antagonists of the Apelin (APJ) receptor. Probe Reports from the NIH Molecular Libraries Program [Internet]. 2013.
