Affinage

EDNRA

Endothelin-1 receptor · UniProt P25101

Length
427 aa
Mass
48.7 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EDNRA encodes the endothelin type A receptor (ET(A)), a Gαq-coupled G protein-coupled receptor that, upon binding endothelin-1 (or endothelin-2), drives vasoconstriction, vascular and cardiac structural remodeling, fibrosis, cell proliferation, and survival across vascular, cardiac, renal, neuronal, endocrine, and tumor contexts (PMID:9863648, PMID:36901906). The proximal signaling output is dissected most fully in human cardiac fibroblasts, where ligand-activated ET(A) signals through Gαq and ERK1/2 to drive proliferation and myofibroblast differentiation with α-SMA and collagen I synthesis (PMID:36901906); in neuroblastoma cells ET(A) couples to both PTX-insensitive IP3-mediated Ca2+ mobilization from intracellular stores and a PTX-sensitive Ca2+ influx and inhibition of cAMP formation (PMID:9863648). Through these cascades ET(A) inhibits ion channels — L-type voltage-sensitive Ca2+ channels in cerebellar granule neurons (PMID:9716711), K_ATP channels underlying hypoxic pulmonary vasoconstriction (PMID:10710514), and voltage-gated Kv channels in pulmonary artery smooth muscle (PMID:10409216) — and engages PKC- and Rho-kinase-dependent contraction (PMID:10690956, PMID:20412427). In the heart, ET(A) mediates hypertrophy and remodeling: cardiac-specific ET(A) knockout protects against cold-stress hypertrophy, contractile dysfunction, ROS generation and apoptosis, abolishing downstream GSK3β/GATA4/CREB activation (PMID:22442497), and ET(A) drives post-infarct MMP activation and TGF-β1-dependent collagen deposition (PMID:11179039, PMID:11208696). In the kidney, ET(A) specifically regulates the ENaC-dependent component of collecting duct sodium transport and modulates NOS1 expression (PMID:23698114, PMID:17892518). In cancer, ET(A) confers PI3K/Akt-dependent apoptosis resistance (PMID:16581180) and forms a STAT3-EDN1 positive feedback loop promoting colorectal cancer proliferation and migration (PMID:36453252). An activating EDNRA Ser420Thr mutation segregates with familial ACTH-independent macronodular adrenal hyperplasia (PMID:23754170). ET(A) localizes predominantly to the plasma membrane and desensitizes more slowly than ET(B), with the two receptors functionally cross-regulating one another (PMID:16740992, PMID:28223322).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1997 Medium

    Established that ET(A) is the receptor through which endothelin-1 drives vascular hypertrophy and cardiomyocyte growth, linking the receptor to structural remodeling rather than acute tone alone.

    Evidence Selective ET(A) antagonism (LU135252) in an angiotensin II rat model with vascular morphometry, plus pharmacological dissection in isolated rabbit ventricular cardiomyocytes

    PMID:9125673 PMID:9315552

    Open questions at the time
    • Did not resolve the intracellular signaling cascade linking ET(A) to growth
    • Cardiomyocyte study implicated both ET(A) and ET(B), leaving relative contributions unsettled
  2. 1998 High

    Defined the proximal G protein coupling of ET(A), showing dual Ca2+-handling mechanisms and cAMP inhibition, and showed receptor-specific modulation of neuronal Ca2+ channels.

    Evidence Multimodal in vitro dissection (Ca2+ imaging, IP accumulation, cAMP, binding, PTX) in ET(A)-only SK-N-MC cells and patch-clamp of cerebellar granule neurons

    PMID:9453352 PMID:9716711 PMID:9863648

    Open questions at the time
    • Did not identify the specific Gαq vs Gαi isoforms in native tissue
    • PLD and other effector arms only partially mapped
  3. 2000 Medium

    Connected ET(A) signaling to K_ATP channel inhibition as the mechanism of hypoxic pulmonary vasoconstriction and to PKC-dependent endocrine secretion, broadening the receptor's effector repertoire.

    Evidence Pharmacological epistasis with glibenclamide rescue in perfused rat lungs; PKC inhibitor experiments in mouse pancreatic islets; in vivo neonatal ductus arteriosus closure model

    PMID:10690956 PMID:10710514 PMID:14607269

    Open questions at the time
    • Direct biochemical link between ET(A) and channel gating not established
    • Developmental ductus role inferred pharmacologically rather than by tissue-specific genetics
  4. 2001 Medium

    Established ET(A) as a driver of cardiac and vascular pathological remodeling through MMP activation and TGF-β1-dependent fibrosis, and confirmed its contribution to human coronary vasoconstrictor tone.

    Evidence Selective antagonists (sitaxsentan, A-127722, BQ-123) in rat post-MI and DOCA-salt models with zymography, histology and TGF-β1 quantification; intracoronary BQ-123 infusion in patients

    PMID:11179039 PMID:11208696 PMID:11717152

    Open questions at the time
    • Cell-type origin of fibrotic signaling not resolved in vivo
    • Did not define the kinase cascade upstream of MMP/TGF-β1
  5. 2006 Medium

    Showed ET(A) couples to PI3K/Akt survival signaling and characterized its plasma membrane localization and slow desensitization relative to ET(B), establishing receptor-level regulatory distinctions.

    Evidence PI3K/Akt pathway inhibition with paclitaxel apoptosis assays in RCC lines; immunocytochemistry and Ca2+ desensitization kinetics in transfected HEK293 cells

    PMID:16581180 PMID:16740992

    Open questions at the time
    • Desensitization machinery (GRK/arrestin) not identified
    • Survival signaling characterized only in cancer cell lines
  6. 2013 High

    Defined ET(A)'s renal role as the specific regulator of ENaC-dependent collecting duct sodium transport and reported an activating EDNRA mutation in a Mendelian adrenal disorder.

    Evidence Microperfusion of isolated mouse cortical collecting ducts with benzamil and subtype-selective antagonists; whole exome sequencing of a familial AIMAH pedigree

    PMID:23698114 PMID:23754170

    Open questions at the time
    • EDNRA Ser420Thr was identified by sequencing without functional validation
    • Signaling linking ET(A) to ENaC regulation not fully mapped
  7. 2017 High

    Revealed functional cross-talk in which ET(A) blockade unmasks ET(B) overstimulation, increasing vascular permeability and fluid retention, clarifying receptor interplay in vivo.

    Evidence Selective vs dual antagonists, Brattleboro rats, and isolated vessel permeability experiments in rats

    PMID:28223322

    Open questions at the time
    • Molecular basis of the ET(A)/ET(B) cross-regulation not defined
    • Human relevance of the permeability effect not directly tested
  8. 2019 High

    Identified a discrete ET(A)-PKA-TRPA1 axis as a peripheral pain-sensitization mechanism, extending ET(A) signaling into nociception.

    Evidence Ca2+ imaging, patch clamp, ETAR/TRPA1 co-localization in DRG neurons, and behavioral pharmacology in mice

    PMID:30990108

    Open questions at the time
    • Whether PKA acts directly on TRPA1 vs intermediate substrates not resolved
    • Contribution to clinical pain states not established
  9. 2023 High

    Fully dissected the Gαq/ERK1/2 pathway driving ET(A)-dependent cardiac fibroblast proliferation and myofibroblast differentiation, and defined a STAT3/EDN1 feedback loop in colorectal cancer.

    Evidence Selective G-protein and ERK1/2 inhibitors with proliferation and marker assays in human cardiac fibroblasts; phosphokinase array, ChIP and promoter assays in CRC cell lines

    PMID:36453252 PMID:36901906

    Open questions at the time
    • In vivo validation of the Gαq/ERK1/2 fibroblast axis pending
    • STAT3/EDN1 loop demonstrated in cell lines only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EDNRA selectively partitions among its multiple downstream effectors (Gαq/IP3, PKC, Rho-kinase, PI3K/Akt, ERK1/2, channel modulation) in a tissue- and ligand-specific manner remains undefined.
  • No structural model of ligand- or context-dependent effector bias
  • Determinants of ET(A) vs ET(B) coupling switching during disease not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-397014 Muscle contraction 2 R-HSA-382551 Transport of small molecules 1
Partners
EDN1STAT3TRPA1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ET(A) receptor mediates angiotensin II-induced vascular hypertrophy: angiotensin II increases tissue endothelin-1 in mesenteric arteries, and selective ET(A) receptor antagonism with LU135252 prevents changes in vascular geometry (media thickness, media/lumen ratio, cross-sectional area) in basilar and small mesenteric arteries. In vivo rat model with selective ET(A) antagonist LU135252; vascular morphometry; tissue ET-1 measurement Circulation Medium 9315552
1998 ET(A) receptor blockade in salt-sensitive Dahl hypertensive rats normalizes vascular ET-1 protein content, prevents aortic hypertrophy, and restores NO-mediated endothelium-dependent relaxation, establishing ET(A) receptor as the mediator of ET-1-driven vascular structural changes and endothelial dysfunction in salt-sensitive hypertension. In vivo Dahl rat model; selective ET(A) antagonist LU135252; aortic tissue weight, vascular reactivity of isolated aortic rings, radioimmunoassay for ET-1 protein Hypertension Medium 9453352
2000 ET(A) receptor mediates hypoxic pulmonary vasoconstriction (HPV) through inhibition of ATP-sensitive K+ (K_ATP) channel activity: ET(A) antagonist BQ-123 inhibited HPV in intact rats and blood-perfused lungs, and this inhibition was prevented by the K_ATP channel blocker glibenclamide. In vivo rat and isolated blood-perfused/PSS-perfused rat lung preparations; selective ET(A) antagonist BQ-123 and ET(B) antagonist BQ-788; K_ATP blocker glibenclamide American journal of physiology. Lung cellular and molecular physiology Medium 10710514
1998 ET(A) receptor stimulation in SK-N-MC neuroblastoma cells (which express only ET(A) receptors) increases intracellular Ca2+ via two mechanisms: a pertussis toxin (PTX)-insensitive, IP3-mediated Ca2+ mobilization from intracellular stores, and a PTX-sensitive influx of extracellular Ca2+. ET(A) receptor also couples to inhibition of cAMP formation via a PTX-sensitive pathway. Fura-2 Ca2+ imaging, [3H]-inositol phosphate accumulation, cAMP assay, [125I]-ET-1 binding, RT-PCR for receptor subtypes, pertussis toxin pretreatment, selective antagonists BQ-123 and BQ-788 in SK-N-MC cells British journal of pharmacology High 9863648
1998 ET(A) receptor activation in rat cerebellar granule neurons inhibits L-type voltage-sensitive Ca2+ channels: ET-1 decreased open probability and frequency of channel opening in cell-attached patches; this effect was blocked by the ET(A) antagonist BQ-123 but not by the ET(B) agonist sarafotoxin 6c. Perforated-patch and cell-attached patch clamp recordings of rat cerebellar granule neurons; selective ET(A) antagonist BQ-123; selective ET(B) agonist sarafotoxin 6c Pflugers Archiv High 9716711
2001 ET(A) receptor activation mediates matrix metalloproteinase (MMP-1, MMP-2, MMP-9) activation in myocardium remote from infarct post-MI, and ET(A) receptor blockade with sitaxsentan prevents MMP activation and left ventricular dilation, establishing ET(A) as a driver of chronic post-MI remodeling via MMP activity. Rat post-MI model; selective ET(A) antagonist sitaxsentan; zymographic MMP activity assays; LV pressure-volume relationships (Langendorff); TIMP-1 expression American journal of physiology. Heart and circulatory physiology Medium 11179039
2001 ET(A) receptor mediates cardiac fibrosis in DOCA-salt hypertensive rats by upregulating procollagen I and III mRNA synthesis and TGF-β1 expression; ET(A) receptor antagonism with A-127722 prevents interstitial and perivascular collagen deposition and normalizes TGF-β1 protein. DOCA-salt rat model; selective ET(A) antagonist A-127722; Sirius red histology; procollagen I/III and TGF-β1 mRNA by Northern/RT-PCR; TGF-β1 protein quantification Circulation Medium 11208696
2001 ET(A) receptor activation mediates vasoconstriction in human coronary arteries contributing to basal coronary vasoconstrictor tone and endothelial dysfunction: intracoronary BQ-123 (ET(A) antagonist) dilated coronary arteries and improved acetylcholine-induced vasodilation in dysfunctional segments. Intracoronary infusion of BQ-123 in patients; epicardial diameter (Doppler) and coronary vascular resistance measurement; arteriovenous ET-1 levels Circulation research Medium 11717152
2001 ET(A) receptor mediates ET-1-induced increases in intracellular Ca2+ in nociceptor-like neurons (ND7/104 cells): BQ-123 dose-dependently inhibited ET-1-induced Ca2+ transients with IC50=20 nM, while ET(B) antagonist BQ-788 had no effect, demonstrating ET(A)-dependent Ca2+ release from intracellular stores. Fura-2 Ca2+ imaging in ND7/104 neuroblastoma-DRG hybrid cells; selective ET(A) antagonist BQ-123 and ET(B) antagonist BQ-788 Neuroreport Medium 11726808
1999 In hypoxic hypertensive rat pulmonary artery smooth muscle cells (PASMC), ET-1-mediated inhibition of voltage-gated K+ (Kv) channels switches coupling from ET(B) to ET(A) receptors during chronic hypoxia, while maximum Kv current inhibition remains 12-18%; this receptor-coupling switch accompanies reduced Kv current density. Whole-cell patch clamp and indo-1 single-cell Ca2+ fluorescence in isolated rat PASMC; normotensive vs. chronically hypoxic hypertensive rats; selective ET(A) and ET(B) antagonists The American journal of physiology Medium 10409216
2006 ET(A) receptor promotes cell survival in renal cell carcinoma (RCC) by inhibiting paclitaxel-induced apoptosis via the PI3-kinase/Akt pathway; ET-1 binding to ET(A) activates PI3K/Akt signaling to confer apoptosis resistance. RCC cell lines; ET(A) receptor expression by RT-PCR, quantitative RT-PCR, and high-affinity binding; apoptosis assay with paclitaxel ± ET-1; PI3K/Akt pathway inhibition; EDNRB methylation analysis Cancer letters Medium 16581180
2006 ET(A) receptor in HEK 293 cells localizes predominantly to the plasma membrane (83% co-localization with pan-cadherin), desensitizes more slowly than ET(B) (t1/2=48 vs. 21 s for ET-1-induced Ca2+ responses), and co-expression of ET(A) and ET(B) receptors eliminates receptor desensitization and redistributes ET(B) to the plasma membrane. Immunocytochemistry with plasma membrane marker pan-cadherin; Fura-2 Ca2+ imaging for desensitization kinetics; HEK 293 cells transfected with ET(A) and/or ET(B) receptors Experimental biology and medicine Medium 16740992
2007 ET(A) receptor activation in inner medullary collecting duct (IMCD) cells specifically upregulates NOS1 (neuronal NOS) protein expression without affecting NOS2 or NOS3; this was confirmed in ET(B)-deficient sl/sl rats which showed elevated NOS1 protein in renal inner medulla (consistent with constitutive ET(A) activation), while NOS1 enzymatic activity paradoxically decreased. Cultured IMCD-3 cells with exogenous ET-1 and ET(A)/ET(B) selective antagonists; Western blot for NOS isoforms; NOS enzymatic activity assay; ET(B)-deficient homozygous (sl/sl) rats as in vivo model Acta physiologica Medium 17892518
2010 EDNRA (ET(A) receptor) mediates the contractile effect of EDN2 (endothelin-2) in the rat ovary: isometric tension analysis showed EDN2-induced contraction was blocked by the EDNRA antagonist BQ123 but not by the EDNRB antagonist BQ788; ECE1 (not ECE2) mediates ovarian endothelin production before ovulation. Isometric tension analysis of isolated rat ovarian tissue; selective ET(A) antagonist BQ123 and ET(B) antagonist BQ788; RT-PCR for ECE1/ECE2 in granulosa cells; endothelin immunoassay Reproduction, fertility, and development Medium 20450830
2012 Cardiac-specific knockout of ET(A) receptor (ETAKO mice) protects against cold stress-induced cardiac hypertrophy, contractile dysfunction, ROS generation, and apoptosis, establishing ET(A) receptor as a mediator of cold exposure-induced cardiac remodeling; ET(A) knockout obliterated cold-stress-induced downregulation of TRPV1 and PGC1α and activation of GSK3β/GATA4/CREB. Cardiac-specific ET(A) receptor knockout mice (ETAKO) vs. WT; cold exposure (4°C, 2 and 5 weeks); echocardiography; myocyte contractility and Ca2+ measurements; Western blotting for TRPV1, PGC1α, UCP2, HSP90, GSK3β, GATA4, CREB; ROS/superoxide measurement; TRPV1 agonist/antagonist experiments; GSK3β inhibitor Journal of molecular cell biology High 22442497
2017 ETA receptor blockade induces exaggerated fluid retention and increased vascular permeability by allowing ET(B) receptor overstimulation: selective ETA antagonism increased plasma volume, vascular permeability, and activated arginine vasopressin and aldosterone release, effects prevented by co-administration of ET(B) antagonist. Isolated vessel experiments confirmed ET(A) blockade increases vascular permeability via ET(B) receptor overstimulation. Rat in vivo studies with selective ETA antagonists (sitaxentan, ambrisentan) and dual antagonists (bosentan, macitentan); hematocrit/hemoglobin measurement; plasma volume expansion; Brattleboro rats and AVP receptor antagonist; isolated vessel permeability experiments The Journal of pharmacology and experimental therapeutics High 28223322
2002 ET(A) and ET(B) receptors both promote proliferation of human pulmonary artery smooth muscle cells (PASMCs): ET-1 stimulated DNA synthesis via both receptor subtypes, and ET(B) receptor stimulation specifically reduced intracellular cAMP levels in PASMCs. In vitro autoradiography; [125I]-ET-1 binding; DNA synthesis assay; cAMP measurement in human PASMCs; selective ET(A) and ET(B) antagonists American journal of respiratory and critical care medicine Medium 11818328
2013 ET-1 inhibits sodium reabsorption (JNa) in the mouse cortical collecting duct (CCD) via both ETA and ETB receptor-mediated pathways; specifically, only ETA receptor blockade restored the benzamil-sensitive (ENaC-mediated) component of JNa, indicating ETA receptor specifically regulates ENaC-dependent Na+ transport. In vitro microperfusion of isolated mouse cortical and outer medullary collecting ducts; benzamil (ENaC blocker); selective ET(A) and ET(B) receptor antagonists; transepithelial Na+ flux measurement American journal of physiology. Renal physiology High 23698114
2019 ETAR (ET(A) receptor) sensitizes TRPA1 channels via a PKA-dependent pathway in primary sensory neurons: ET-1 sensitized TRPA1-mediated Ca2+ responses and channel currents in HEK293 cells and dorsal root ganglion (DRG) neurons; ETAR colocalized with TRPA1 in DRG neurons; pharmacological blocking of ETAR, PKA, and TRPA1 attenuated ET-1-induced mechanical hyperalgesia in mice. Ca2+ imaging, electrophysiology (patch clamp), immunostaining for ETAR/TRPA1 co-localization in DRG neurons; HEK293 cells expressing TRPA1 ± ETAR; selective ETAR antagonist; PKA inhibitor; animal behavioral assay Molecular pain High 30990108
2023 ET-1 induces cardiac fibroblast proliferation and myofibroblast differentiation (α-SMA and collagen I synthesis) through the ETAR subtype via a Gαq/ERK1/2 signaling pathway; inhibition of Gαq (but not Gαi or Gβγ) blocked these effects, and ERK1/2 was required for ETAR/Gαq-axis-induced proliferation and marker expression. Human cardiac fibroblasts; selective ETAR and ETB antagonists (ambrisentan, bosentan); Gα subunit inhibitors; ERK1/2 inhibitors; Western blot for α-SMA and collagen I; cell proliferation assay; myofibroblast reversal assay International journal of molecular sciences High 36901906
1997 ET-1-induced hypertrophy of isolated adult rabbit ventricular cardiomyocytes is mediated by both ET(A) and ET(B) receptor subtypes and involves PKC activation: ET(A) antagonists BQ123 and PD155080, and ET(B) antagonist BQ788, all reduced [14C]phenylalanine incorporation; PKC inhibitor bisindolylmaleimide reduced ET-1-induced RNA and protein synthesis. Isolated adult rabbit ventricular cardiomyocytes; [14C]phenylalanine and [14C]uridine incorporation assays; selective ET(A) (BQ123, PD155080) and ET(B) (BQ788) antagonists; PKC inhibitor BIM Journal of cardiovascular pharmacology Medium 9125673
1997 ET(A) receptor plays the predominant role in mediating ET-1-induced catecholamine (CA) secretion from the canine adrenal medulla in vivo: low-dose BQ-123 (ET(A) antagonist) inhibited the CA response by ~80%, high-dose virtually abolished it, while BQ-788 (ET(B) antagonist) at low dose had no significant effect. Anesthetized dogs; local intra-adrenal ET-1 infusion; adrenal venous plasma catecholamine measurement by HPLC; dose-dependent BQ-123 and BQ-788 pretreatment The American journal of physiology Medium 9140032
2008 ET(A) receptor mediates ET-1-stimulated lipolysis in human adipocytes: a 24-hour incubation with an ET(A) receptor agonist (but not ET(B) agonist) increased lipolysis by ~50% in primary human adipocyte cultures; ET(A) receptor protein (but not mRNA) expression is increased in subcutaneous adipose tissue in obesity. Primary human adipocyte cultures; ET(A) and ET(B) receptor agonists; lipolysis assay; ET(A)R and ET(B)R protein expression by Western blot; mRNA by qPCR in 37 subjects International journal of obesity Medium 18982011
2000 ET(A) receptor activation is required for postnatal ductus arteriosus (DA) closure in rats: pharmacological ET(A) blockade in neonatal rat pups inhibited DA closure at 3 hours after birth; gestational ET(A) blockade replicated ET(A) gene knockout phenotypes including craniofacial abnormalities (mid-gestation) and patent DA (late gestation). Neonatal rat in vivo; ET(A)-selective antagonists administered intraperitoneally; DA diameter measurement; comparison with ET(A) knockout phenotype; indomethacin (NSAID tocolysis) DA constriction model Life sciences Medium 14607269
2000 ET(A) receptor mediates ET-1-potentiated insulin secretion in mouse pancreatic islets via PKC: ET(A) antagonist BQ123 blocked ET-1-stimulated insulin secretion at 1–10,000 nM; PKC inhibitor calphostin C and PKC downregulation abolished the insulinotropic effect of ET-1; ET(B) agonist BQ3020 had no effect. Isolated mouse islets of Langerhans; insulin secretion assay; selective ET(A) antagonist BQ123; ET(B) agonist BQ3020; PKC activator TPA; PKC inhibitor calphostin C; PKC downregulation by TPA pretreatment; Wortmannin (PI3K inhibitor) Metabolism Medium 10690956
2022 EDNRA promotes colorectal cancer (CRC) progression through a positive feedback loop with EDN1 mediated by STAT3: EDNRA knockdown suppressed STAT3 phosphorylation; STAT3 silencing decreased EDN1 and EDNRA expression; STAT3 directly bound EDNRA and EDN1 promoters (shown by ChIP and promoter assays); EDNRA overexpression promoted cell proliferation and migration. CRC cell lines; phosphokinase array; EDNRA knockdown/overexpression; STAT3 silencing; ChIP assay; promoter assay; proliferation and migration assays; macitentan (EDNRA antagonist) treatment International journal of oncology Medium 36453252
2010 ET-1 induces contraction of female rat internal pudendal and clitoral arteries through the ET(A) receptor and Rho-kinase activation: ET(A)R antagonist atrasentan reduced ET-1-induced contraction and shifted pD2; Rho-kinase inhibitor Y-27632 also shifted ET-1 pD2; ET(A)R, RhoA, and Rho-kinase proteins were detected by Western blot in IPA. Isolated artery myograph experiments; selective ET(A)R antagonist atrasentan; Rho-kinase inhibitor Y-27632; Western blot and real-time PCR for ET(A)R, ET(B)R, RhoA, Rho-kinase in rat IPA The journal of sexual medicine Medium 20412427
2021 Autoantibodies targeting ETAR (ET(A) receptor) in scleroderma renal crisis activate the MAPK pathway and downstream Ets-1 transcription factor in endothelial cells, inducing endothelial proliferation and tissue factor (TF) expression; ETAR inhibitors/shRNA abrogated these effects, confirming ETAR-dependent signaling. Patient-derived IgG from scleroderma renal crisis applied to endothelial cells; MAPK pathway activation assay; Ets-1 immunostaining; TF promoter assay; ETAR inhibitors and shRNA knockdown; endothelial cell proliferation assay; TF inhibition International journal of molecular sciences Medium 35008670
2013 EDNRA Ser420Thr mutation was identified as a causative mutation for familial ACTH-independent macronodular adrenal hyperplasia (AIMAH) by whole exome sequencing and disease network analysis in an affected pedigree. Whole exome sequencing of familial AIMAH pedigree; variant prioritization via disease network analysis; adrenalectomy tissue samples Familial cancer Low 23754170
1998 ET(A) receptor activation in rat cortical astrocytes mediates phospholipase D (PLD) activation: approximately 20% of ET-1-induced PLD activation was mediated by ET(A) receptors (remaining ~80% by ET(B) receptors); after ET(B) receptor desensitization, the remaining ET-1-induced PLD response was fully blocked by BQ-123 (ET(A) antagonist). Primary rat cortical astrocyte cultures; [32P]phosphatidylbutanol formation assay for PLD activity; selective ET(A) antagonist BQ-123 and ET(B) antagonist BQ-788; receptor desensitization paradigms British journal of pharmacology Medium 9756390

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Angiotensin II increases tissue endothelin and induces vascular hypertrophy: reversal by ET(A)-receptor antagonist. Circulation 293 9315552
2007 Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annual review of pharmacology and toxicology 243 17002597
2002 ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. American journal of respiratory and critical care medicine 238 11818328
1998 ET(A) receptor blockade prevents increased tissue endothelin-1, vascular hypertrophy, and endothelial dysfunction in salt-sensitive hypertension. Hypertension (Dallas, Tex. : 1979) 157 9453352
2001 Myocardial fibrosis in DOCA-salt hypertensive rats: effect of endothelin ET(A) receptor antagonism. Circulation 123 11208696
2001 Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism. British journal of cancer 105 11742499
2001 ET(A) receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats. Hypertension (Dallas, Tex. : 1979) 103 11408393
2011 Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk. Proceedings of the National Academy of Sciences of the United States of America 95 22106312
2014 Maternal PRKAA1 and EDNRA genotypes are associated with birth weight, and PRKAA1 with uterine artery diameter and metabolic homeostasis at high altitude. Physiological genomics 94 25225183
2000 ABT-627, an endothelin ET(A) receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain. European journal of pharmacology 93 10657544
2017 Endothelin ETA Receptor Blockade, by Activating ETB Receptors, Increases Vascular Permeability and Induces Exaggerated Fluid Retention. The Journal of pharmacology and experimental therapeutics 74 28223322
2000 Mechanism of hypoxic pulmonary vasoconstriction involves ET(A) receptor-mediated inhibition of K(ATP) channel. American journal of physiology. Lung cellular and molecular physiology 70 10710514
1998 Selective ET(A) receptor antagonism reduces neointimal hyperplasia in a porcine coronary stent model. Circulation 61 9657476
2001 Coronary vasodilation and improvement in endothelial dysfunction with endothelin ET(A) receptor blockade. Circulation research 59 11717152
2012 Cardiac-specific knockout of ET(A) receptor mitigates low ambient temperature-induced cardiac hypertrophy and contractile dysfunction. Journal of molecular cell biology 58 22442497
2001 ET(A)-receptor blockade prevents matrix metalloproteinase activation late postmyocardial infarction in the rat. American journal of physiology. Heart and circulatory physiology 55 11179039
1997 Selective antagonism of the ET(A) receptor reduces neointimal hyperplasia after balloon-induced vascular injury in pigs. Journal of cardiovascular pharmacology 54 9268219
2006 Endothelin-1 promotes cell survival in renal cell carcinoma through the ET(A) receptor. Cancer letters 53 16581180
2007 Endothelin-1-induced pulmonary vasoreactivity is regulated by ET(A) and ET(B) receptor interactions. Journal of vascular research 52 17495482
2001 Endothelin-1 activates ET(A) receptors to increase intracellular calcium in model sensory neurons. Neuroreport 52 11726808
2013 Androgens influence microvascular dilation in PCOS through ET-A and ET-B receptors. American journal of physiology. Endocrinology and metabolism 51 23921139
1999 The ET(A) receptor blocker LU 135252 prevents chronic transplant nephropathy in the "Fisher to Lewis" model. Journal of the American Society of Nephrology : JASN 49 10215340
1998 Nephroprotection of an ET(A)-receptor blocker (LU 135252) in salt-loaded uninephrectomized stroke-prone spontaneously hypertensive rats. Hypertension (Dallas, Tex. : 1979) 49 9535426
2001 Effects of ET(A) - and ET(B)-receptor antagonists on regional kidney blood flow, and responses to intravenous endothelin-1, in anaesthetized rabbits. Journal of hypertension 44 11593099
2008 Endothelin-1 stimulates human adipocyte lipolysis through the ET A receptor. International journal of obesity (2005) 40 18982011
2002 Chronic ET(A) receptor blockade prevents endothelial dysfunction of small arteries in apolipoprotein E-deficient mice. Cardiovascular research 40 11827700
2002 Cardioprotection by long-term ET(A) receptor blockade and ACE inhibition in rats with congestive heart failure: mono- versus combination therapy. Cardiovascular research 39 12062365
2013 Endothelin-1 inhibits sodium reabsorption by ET(A) and ET(B) receptors in the mouse cortical collecting duct. American journal of physiology. Renal physiology 38 23698114
2001 Renal endothelin ET(A)/ET(B) receptor imbalance differentiates salt-sensitive from salt-resistant spontaneous hypertension. Hypertension (Dallas, Tex. : 1979) 38 11230285
2004 Effects of selective endothelin ET(A) receptor antagonists on endothelin-1-induced potentiation of cancer pain. European journal of pharmacology 37 15178362
2000 Selective ET(A) receptor antagonism with ABT-627 attenuates all renal effects of endothelin in humans. Journal of the American Society of Nephrology : JASN 37 10906163
1998 Systemic and renal effects of an ET(A) receptor subtype-specific antagonist in healthy subjects. British journal of pharmacology 37 9692778
2000 Synergistic effects of AT(1) and ET(A) receptor blockade in a transgenic, angiotensin II-dependent, rat model. Hypertension (Dallas, Tex. : 1979) 36 10775574
2003 Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension. Clinical genetics 35 14616768
2001 TBC3711, an ET(A) receptor antagonist, reduces neonatal hypoxia-induced pulmonary hypertension in piglets. Pediatric research 35 11518825
2002 Hypertension induced by blockade of ET(B) receptors in conscious nonhuman primates: role of ET(A) receptors. American journal of physiology. Heart and circulatory physiology 33 12234809
1999 Endothelin ET(A) receptor blockade prevents the progression of renal failure and hypertension in uraemic rats. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 33 10462266
1999 Cardiac microvasculature in DOCA-salt hypertensive rats : effect of endothelin ET(A) receptor antagonism. Hypertension (Dallas, Tex. : 1979) 33 10523363
2016 Genomic amplification of the caprine EDNRA locus might lead to a dose dependent loss of pigmentation. Scientific reports 32 27329507
2000 Influence of dual ET(A)/ET(B)-receptor blockade on coronary responses to treadmill exercise in dogs. Journal of applied physiology (Bethesda, Md. : 1985) 32 11053360
2010 Production and binding of endothelin-2 (EDN2) in the rat ovary: endothelin receptor subtype A (EDNRA)-mediated contraction. Reproduction, fertility, and development 31 20450830
2009 EDNRA variants associate with smooth muscle mRNA levels, cell proliferation rates, and cystic fibrosis pulmonary disease severity. Physiological genomics 31 20028935
2005 Comparison of selective ET(A) and ET(B) receptor antagonists in patients with chronic heart failure. European journal of heart failure 31 15642529
2003 Et-A receptor antagonist BQ123 prevents radiocontrast media-induced renal medullary hypoxia. Acta radiologica (Stockholm, Sweden : 1987) 31 12631011
2002 Gender differences in vascular expression of endothelin and ET(A)/ET(B) receptors, but not in calcium handling mechanisms, in deoxycorticosterone acetate-salt hypertension. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 30 12219177
2014 Selective ET(A) receptor blockade protects against cisplatin-induced acute renal failure in male rats. European journal of pharmacology 29 24632086
2009 Role of ET(A) and ET(B) endothelin receptors on endothelin-1-induced potentiation of nociceptive and thermal hyperalgesic responses evoked by capsaicin in rats. Neuroscience letters 29 19429182
2008 Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation. Journal of pharmacological sciences 29 18270470
2000 Endothelin ET(A) receptor antagonism attenuates the pressor effects of nicotine in rats. European journal of pharmacology 28 10822051
2023 Endothelin-1 Induces Cell Proliferation and Myofibroblast Differentiation through the ETAR/Gαq/ERK Signaling Pathway in Human Cardiac Fibroblasts. International journal of molecular sciences 27 36901906
2002 Expression of ET(A) and ET(B) receptor mRNA in human cerebral arteries. British journal of neurosurgery 27 12046734
2017 Dual ETA/ETB blockade with macitentan improves both vascular remodeling and angiogenesis in pulmonary arterial hypertension. Pulmonary circulation 26 29064353
2007 Differential effects of ET(A) and ET(B) receptor antagonism on oxidative stress in type 2 diabetes. Vascular pharmacology 26 17597010
2006 ET-1 Lys198Asn and ET(A) receptor H323H polymorphisms in heart failure. A case-control study. Cardiology 26 16582543
2005 Reversal of cardiac dysfunction by selective ET-A receptor antagonism. British journal of pharmacology 26 16151437
2015 Associations of EDNRA and EDN1 polymorphisms with carotid intima media thickness through interactions with gender, regular exercise, and obesity in subjects in Taiwan: Taichung Community Health Study (TCHS). BioMedicine 25 26040574
2013 Whole exome sequencing identifies mutation of EDNRA involved in ACTH-independent macronodular adrenal hyperplasia. Familial cancer 25 23754170
2006 Differential trafficking and desensitization of human ET(A) and ET(B) receptors expressed in HEK 293 cells. Experimental biology and medicine (Maywood, N.J.) 25 16740992
2013 Addition of ET(A) receptor blockade increases renoprotection provided by renin-angiotensin system blockade in 5/6 nephrectomized Ren-2 transgenic rats. Life sciences 24 24373834
1998 ET(A) and ET(B) specific ligands synergistically antagonize endothelin-1 binding to an atypical endothelin receptor in primary rat astrocytes. Journal of neurochemistry 24 9453540
2017 Upregulation of the endothelin A (ETA) receptor and its association with neurodegeneration in a rodent model of glaucoma. BMC neuroscience 23 28249604
2014 High expression of GEM and EDNRA is associated with metastasis and poor outcome in patients with advanced bladder cancer. BMC cancer 23 25175477
2007 Endothelin(A) (ET(A)) and ET(B) receptor-mediated regulation of nitric oxide synthase 1 (NOS1) and NOS3 isoforms in the renal inner medulla. Acta physiologica (Oxford, England) 23 17892518
2003 Pharmacological knockout of endothelin ET(A) receptors. Life sciences 23 14607269
2000 Selective ET(A) antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives. Journal of medicinal chemistry 23 10715156
2018 Baicalein Ameliorates Pulmonary Arterial Hypertension Caused by Monocrotaline through Downregulation of ET-1 and ETAR in Pneumonectomized Rats. The American journal of Chinese medicine 22 29737212
2006 Endothelin receptor antagonism in pulmonary arterial hypertension--a role for selective ET(A) inhibition? Current medical research and opinion 22 17166339
2000 ET(A)-receptor blockade and ET(B)-receptor stimulation in experimental congenital diaphragmatic hernia. American journal of physiology. Lung cellular and molecular physiology 22 10781422
1997 Involvement of endothelin (ET)A and ETB receptors in the hypertrophic effects of ET-1 in rabbit ventricular cardiomyocytes. Journal of cardiovascular pharmacology 22 9125673
2019 Endothelins (EDN1, EDN2, EDN3) and their receptors (EDNRA, EDNRB, EDNRB2) in chickens: Functional analysis and tissue distribution. General and comparative endocrinology 21 31351053
2005 ET(A) receptor blockade prevents renal dysfunction in salt-sensitive hypertension induced by sensory denervation. American journal of physiology. Heart and circulatory physiology 21 15994858
2000 Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release. Naunyn-Schmiedeberg's archives of pharmacology 21 10961375
1998 Involvement of ET(A) and ET(B) receptors in the activation of phospholipase D by endothelins in cultured rat cortical astrocytes. British journal of pharmacology 21 9756390
1998 Mechanism of ET(A)-receptor stimulation-induced increases in intracellular Ca2+ in SK-N-MC cells. British journal of pharmacology 21 9863648
2014 Effect of SNP polymorphisms of EDN1, EDNRA, and EDNRB gene on ischemic stroke. Cell biochemistry and biophysics 20 24633486
2022 The EDN1/EDNRA/β‑arrestin axis promotes colorectal cancer progression by regulating STAT3 phosphorylation. International journal of oncology 19 36453252
2019 ETAR and protein kinase A pathway mediate ET-1 sensitization of TRPA1 channel: A molecular mechanism of ET-1-induced mechanical hyperalgesia. Molecular pain 19 30990108
1999 Enhanced ET(A)-receptor-mediated inhibition of K(v) channels in hypoxic hypertensive rat pulmonary artery myocytes. The American journal of physiology 19 10409216
1998 Endothelin-1 inhibits voltage-sensitive Ca2+ channels in cultured rat cerebellar granule neurones via the ET-A receptor. Pflugers Archiv : European journal of physiology 19 9716711
2022 High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ETA/ETB Receptor and mTOR Pathway. International journal of molecular sciences 18 36430296
2021 Effect of ET-A blockade on portal pressure and hepatic arterial perfusion in patients with cirrhosis: A proof of concept study. Liver international : official journal of the International Association for the Study of the Liver 18 33295121
2010 Endothelin-1 induces contraction of female rat internal pudendal and clitoral arteries through ET(A) receptor and rho-kinase activation. The journal of sexual medicine 18 20412427
1997 Role of ET(A) and ET(B) receptors in endothelin-1-induced adrenal catecholamine secretion in vivo. The American journal of physiology 18 9140032
2017 miR-200c regulates the proliferation, apoptosis and invasion of gastric carcinoma cells through the downregulation of EDNRA expression. International journal of molecular medicine 17 29286062
2001 ET(B) receptor-deficient rats exhibit reduced contraction to ET-1 despite an increase in ET(A) receptors. American journal of physiology. Heart and circulatory physiology 17 11709437
2000 Endothelin-1 (ET-1)-potentiated insulin secretion: involvement of protein kinase C and the ET(A) receptor subtype. Metabolism: clinical and experimental 17 10690956
2018 Renoprotective effects of ET(A) receptor antagonists therapy in experimental non-diabetic chronic kidney disease: Is there still hope for the future? Physiological research 16 29947528
2017 Renin-angiotensin system blockade alone or combined with ETA receptor blockade: effects on the course of chronic kidney disease in 5/6 nephrectomized Ren-2 transgenic hypertensive rats. Clinical and experimental hypertension (New York, N.Y. : 1993) 16 28287881
2014 Selective endothelin ETA and dual ET(A)/ET(B) receptor blockade improve endothelium-dependent vasodilatation in patients with type 2 diabetes and coronary artery disease. Life sciences 16 24607773
2006 Dual ET(A)/ET(B) vs. selective ET(A) endothelin receptor antagonism in patients with pulmonary hypertension. European journal of clinical investigation 16 16919004
2000 Combined effects of AT(1) and ET(A) receptor antagonists, candesartan, and A-127722 in DOCA-salt hypertensive rats. General pharmacology 16 11368889
1999 Pharmacology of A-216546: a highly selective antagonist for endothelin ET(A) receptor. European journal of pharmacology 16 10082200
1999 Benzofuro[3,2-b]pyridines as mixed ET(A)/ET(B) and selective ET(B) endothelin receptor antagonists. Bioorganic & medicinal chemistry letters 16 10098676
1998 Role of endothelin ET(A) receptors in the hypertension produced by 4-day L-nitroarginine methyl ester and cyclosporine treatment. European journal of pharmacology 16 9617750
1997 Influence of endothelin ET(A) and ET(B) receptor antagonists on endothelin-induced contractions of the guinea pig isolated gall bladder. Regulatory peptides 16 9163578
2022 MicroRNA-342-3p loaded by human umbilical cord mesenchymal stem cells-derived exosomes attenuates deep vein thrombosis by downregulating EDNRA. Journal of thrombosis and thrombolysis 15 36006542
2021 Autoantibodies Targeting AT1- and ETA-Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor. International journal of molecular sciences 15 35008670
2018 Antioxidant capacity and polyphenolic content of the Echinocystis lobata (Michx.) Torr. et A.Gray flowers. Pakistan journal of pharmaceutical sciences 15 29625941
2018 Combined hydroxyurea and ETA receptor blockade reduces renal injury in the humanized sickle cell mouse. Acta physiologica (Oxford, England) 15 30144292
2017 Role of endothelin-1 and its receptors, ETA and ETB, in the survival of human vascular endothelial cells. Canadian journal of physiology and pharmacology 15 28732172

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