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Ednra
Ednra Full Name
endothelin receptor type A
Ednra Introduction
The endothelin A receptor (EDNRA) is a member of the G protein-coupled receptor (GPCR) superfamily and plays a crucial role in human physiology and pathophysiology as a key component of the endothelin (ET) system. The endothelin system consists mainly of three isoforms (ET-1, ET-2, ET-3) and two primary receptor subtypes (ET_A and ET_B). Among these, ET-1 is the most potent vasoconstrictor peptide discovered to date, primarily produced by vascular endothelial cells, and EDNRA is its main physiological effector receptor. EDNRA is widely distributed in human tissues and is especially densely expressed on vascular smooth muscle cells. When ET-1 binds to EDNRA on these cells, it activates a series of downstream signaling pathways, such as the phospholipase C (PLC) pathway, leading to an increase in intracellular calcium concentration. This ultimately triggers strong contraction of the smooth muscle cells, resulting in vasoconstriction and elevated blood pressure. Beyond vascular smooth muscle cells, EDNRA is also expressed in cardiomyocytes, fibroblasts, and certain tumor cells.
Figure 1. Scheme of the endothelin system. (Source: Martínez-Díaz I, et al. 2023)
The core functions of EDNRA are primarily mediated through the biological effects of its main ligand, ET-1. Upon binding of ET-1 to EDNRA, in addition to the classic Gq/11 protein-mediated PLC-IP3-Ca2+ pathway causing acute vasoconstriction, it can activate other signaling pathways such as the mitogen-activated protein kinase (MAPK) pathway. This confers a potent mitogenic effect, stimulating the proliferation and migration of vascular smooth muscle cells, fibroblasts, and cancer cells. This pro-proliferative effect is a key element in vascular remodeling and tumor progression. For instance, in prostate cancer cells, ET-1 activation of EDNRA not only promotes cancer cell growth but also stimulates angiogenesis, providing essential nutritional support for tumor growth and metastasis. Furthermore, sustained activation of EDNRA is associated with excessive deposition of extracellular matrix, promoting tissue fibrosis—a process central to ventricular and vascular remodeling in diseases such as heart failure and pulmonary arterial hypertension (PAH).
In the pathophysiology of PAH, ET-1 expression is significantly upregulated. Its binding to EDNRA is considered a central mechanism leading to persistent pulmonary vasoconstriction, excessive proliferation and apoptosis resistance of vascular smooth muscle cells, and vascular wall remodeling and fibrosis. This understanding directly led to the development of endothelin receptor antagonists (ERAs), which have become one of the three cornerstone drug classes for PAH treatment. By blocking the binding of ET-1 to its receptors, ERAs effectively counteract the pathological processes mediated by EDNRA.
Alternate Names for Ednra
EDNRA; endothelin receptor type A; ETA; ET-A; ETAR; ETRA; ETA-R; hET-AR; endothelin-1 receptor; G protein-coupled receptor; endothelin receptor subtype A; endothelin-1-specific receptor;
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