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Pathway Description
Apelin Signaling
Homo sapiens
Signaling Pathway
Created: 2025-05-07
Last Updated: 2025-10-02
The apelin receptor (APJ) is a member of the family A of G-protein coupled receptors (GPCR). Its functions are involved in many different physiological and pathological processes such as fluid homeostasis in addition to cardiovascular and metabolic disorders. The apelin/APJ pathway plays roles in many organs to regulate blood pressure, aid in cardiac contractility, maintain cardiac balance, cell proliferation, and inflammation. The pathway is initiated by the binding of apelin to the apelin receptor. All apelin isoforms are able to elicit a canonical G-mediated inhibition of adenylate cyclase resulting in the inhibition of cAMP. In addition, like most GPCRs, the apelin receptor engages with other G proteins that end in downstream activation of phospholipase C (PLC) and AMP-activated protein kinase (AMPK) pathways. These downstream pathway activations result in various physiological responses associated with the apelin pathway.
References
Apelin Signaling References
Chapman, N. A., Dupré, D. J., & Rainey, J. K. (2014). The apelin receptor: physiology, pathology, cell signalling, and ligand modulation of a peptide-activated class A GPCR. Biochemistry and cell biology = Biochimie et biologie cellulaire, 92(6), 431–440. https://doi.org/10.1139/bcb-2014-0072
Chapman, F.A., Nyimanu, D., Maguire, J.J. et al. The therapeutic potential of apelin in kidney disease. Nat Rev Nephrol 17, 840–853 (2021). https://doi.org/10.1038/s41581-021-00461-z
Hu, G., Wang, Z., Zhang, R., Sun, W., & Chen, X. (2021). The Role of Apelin/Apelin Receptor in Energy Metabolism and Water Homeostasis: A Comprehensive Narrative Review. Frontiers in physiology, 12, 632886. https://doi.org/10.3389/fphys.2021.632886
Estienne, A., Bongrani, A., Froment, P., & Dupont, J. (2021). Apelin and chemerin receptors are G protein-coupled receptors involved in metabolic as well as reproductive functions: Potential therapeutic implications? Current Opinion in Endocrine and Metabolic Research, 16, 86–95. https://doi.org/10.1016/j.coemr.2020.09.005
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