Affinage

EDNRB

Endothelin receptor type B · UniProt P24530

Length
442 aa
Mass
49.6 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EDNRB is a class A G-protein-coupled receptor that binds the endothelin isopeptides ET-1 and ET-3 with approximately equal potency and couples to intracellular Ca2+ mobilization, defining its non-isopeptide-selective pharmacology (PMID:1713452). Crystal structures of ligand-free and ET-1-, ET-3-, and partial-agonist-bound receptor show that transmembrane helices 1, 2, 6, and 7 close around the peptide in an essentially irreversible manner, and that disruption of a water-mediated W6.48–D2.50 interaction propagates conformational change to the cytoplasmic G-protein interface to drive full activation (PMID:27595334, PMID:30413709). Downstream of receptor engagement, EDNRB activates the MAPK cascade and proliferation (PMID:7943276), tyrosine-kinase pathways including FAK and paxillin that regulate the Na+/H+ exchanger NHE3 (PMID:8843705, PMID:10199826), and NOS/cGMP/PKG signaling (PMID:18305094). The receptor exerts opposing vascular actions in vivo, mediating both endothelium-dependent vasodilation and sustained vasoconstriction (PMID:1323294, PMID:8124808). Endothelial EDNRB is the primary clearance site for circulating ET-1 (PMID:20628430) and drives prostaglandin- and NO-dependent depressor tone, vasogenic edema through eNOS–MMP-9–ZO-1 degradation, and modulation of alveolar fluid reabsorption (PMID:10198387, PMID:18948426, PMID:26232046), while renal medullary EDNRB promotes diuresis and natriuresis via a NOS1→cGMP→PKG cascade (PMID:18305094). In neural crest development EDNRB controls enteric progenitor proliferation, migration, and differentiation timing, integrating with RET signaling through PKA and a shared GATA2/SOX10 transcriptional network, with its own expression directly activated by SOX10, ZEB2, GATA2, and NKX2.5 (PMID:14659090, PMID:28063956, PMID:31313802), and it cooperates with Wnt signaling to drive melanocyte stem cell activation and regeneration (PMID:27134165, PMID:28779103). Loss-of-function and dosage-sensitive mutations of EDNRB cause Hirschsprung disease and Waardenburg syndrome type II through failed enteric neuron and melanocyte colonization (PMID:28236341, PMID:9371807), and promoter CpG-island hypermethylation silences EDNRB transcription (PMID:11309363).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1991 High

    Established that EDNRB is a functional endothelin receptor with non-selective isopeptide pharmacology, distinguishing it from the ETA subtype and defining its core signaling output.

    Evidence cDNA cloning and expression in COS cells with radioligand binding and Ca2+ imaging

    PMID:1713452

    Open questions at the time
    • Did not resolve the structural basis of ligand binding
    • G-protein coupling specificity not defined
  2. 1992 High

    Showed that a single EDNRB-selective agonist produces both vasodilation and vasoconstriction in vivo, revealing dual and opposing vascular roles for one receptor.

    Evidence In vivo rat pharmacology with selective ETB agonist sarafotoxin S6c and hemodynamic measurements

    PMID:1323294

    Open questions at the time
    • Cell types responsible for each response not distinguished
    • Downstream signaling mediators undefined
  3. 1993 Medium

    Localized EDNRB protein predominantly to endothelial cells across tissues and quantified tissue-specific ETB:ETA ratios, framing where the receptor acts.

    Evidence Immunohistochemistry, Western blot, and immunoprecipitation with subtype-specific antiserum

    PMID:8476120

    Open questions at the time
    • Single-lab antiserum-based localization
    • Non-endothelial expression sites not fully mapped
  4. 1994 High

    Defined intracellular signaling outputs by showing EDNRB couples to the MAPK cascade and drives proliferation, and that smooth muscle ETB receptors are functionally contractile.

    Evidence CHO cDNA transfection with MAPK and thymidine incorporation assays; human vessel pharmacology with ETB downregulation controls and Northern blot

    PMID:7943276 PMID:8124808

    Open questions at the time
    • Link between MAPK activation and physiological contraction not established
    • G-protein identity not defined
  5. 1999 High

    Connected EDNRB to renal ion transport by showing ETB-specific activation stimulates NHE3 via tyrosine-kinase pathways including FAK/paxillin and direct NHE3 phosphorylation.

    Evidence Na+/H+ antiporter activity, immunoprecipitation, phosphorylation and mobility-shift analyses in OKP cells expressing ETB vs ETA

    PMID:10199826 PMID:8843705

    Open questions at the time
    • Identity of the 210 kDa phosphoprotein mediator unknown
    • Kinase acting directly on NHE3 not identified
  6. 1999 High

    Demonstrated in vivo that endogenous ETB tone lowers blood pressure largely through prostaglandin production, dissecting the depressor mechanism.

    Evidence ETB hypomorphic mice with selective antagonists, indomethacin and L-NMMA, and blood pressure telemetry

    PMID:10198387

    Open questions at the time
    • Cellular source of prostaglandins not pinpointed
    • Relationship to ET clearance not resolved here
  7. 2003 High

    Revealed how EDNRB integrates with RET during enteric nervous system development, identifying PKA as the crosstalk node and demonstrating tissue-restricted genetic epistasis.

    Evidence Primary ENS progenitor assays with PKA pharmacology; two-locus noncomplementation and allelic-series genetics in Ret-null mice

    PMID:12574515 PMID:14659090

    Open questions at the time
    • Molecular basis of opposing migration vs proliferation effects unresolved
    • Direct PKA substrates not identified
  8. 2008 High

    Defined organ-specific EDNRB signaling cascades: NOS1-cGMP-PKG-driven natriuresis in renal medulla, NO-dependent suppression of alveolar Na,K-ATPase, and a mitochondrial apoptotic pathway in retinal cells.

    Evidence In vivo renal infusion and lung perfusion in ETB-deficient rats with NOS/PKG inhibitors; flow cytometry and cytochrome c/JNK assays in RGC-5 cells

    PMID:18305094 PMID:18516102 PMID:18948426

    Open questions at the time
    • Apoptosis pathway shown in a single lab
    • Cell-type specificity of NO source in lung not fully resolved
  9. 2010 High

    Established endothelial EDNRB as the principal clearance receptor for circulating ET-1 using cell-type-specific genetics.

    Evidence Endothelial-specific Cre-lox ETB knockout mice with 125I-ET-1 clearance, autoradiography, and selective antagonist

    PMID:20628430

    Open questions at the time
    • Intracellular fate of internalized ET-1 not traced
    • Contribution to circulating ET-1 setpoint in disease undefined
  10. 2016 High

    Provided the structural mechanism of activation, showing TM1/2/6/7 envelopment of endothelin and propagation of conformational change to the G-protein interface.

    Evidence X-ray crystallography of ligand-free and ET-1-bound EDNRB with mutagenesis and Ca2+ assays

    PMID:27595334

    Open questions at the time
    • No active-state complex with bound G protein
    • Dynamics of irreversible binding not captured
  11. 2016 High

    Showed EDNRB drives melanocyte stem cell proliferation and regeneration in a Wnt-dependent manner, placing it within a niche signaling network.

    Evidence Melanocyte-stem-cell-specific EdnrB knockout, Wnt modulation, and Mc1R mutant rescue in vivo

    PMID:27134165

    Open questions at the time
    • Molecular point of Wnt-EDNRB convergence not defined
    • Downstream effectors in stem cells unidentified
  12. 2017 High

    Connected EDNRB to disease and transcriptional control: WS2-causing mutations impair localization/signaling, EDN3-EDNRB prevents premature ENS differentiation, and SOX10/ZEB2 directly activate the EDNRB promoter.

    Evidence Exome sequencing and cellular assays of WS2 mutations; epilation-induced EDN3 in vivo; ChIP, transactivation, and retroviral rescue in enteric progenitors

    PMID:28063956 PMID:28236341 PMID:28779103

    Open questions at the time
    • WS2 functional studies from a single lab
    • How differentiation timing is mechanistically held in check unresolved
  13. 2019 High

    Mapped the transcriptional regulatory logic explaining RET-EDNRB epistasis, showing GATA2, SOX10, and NKX2.5 directly drive EDNRB in a dose-dependent feedback network shared with RET.

    Evidence ChIP and reporter assays in human and mouse cellular models with animal expression analyses

    PMID:31313802

    Open questions at the time
    • Quantitative dynamics of the feedback loop undefined
    • Tissue specificity of NKX2.5 input not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EDNRB's full active-state signaling complexes (G protein, arrestin) are organized, and how cell-type-specific transcriptional and post-transcriptional control (methylation, miRNA, autophagy) is integrated to set receptor abundance in disease, remains incompletely defined.
  • No active-state G-protein-bound structure in the corpus
  • Integration of methylation, miR-124-3p, and AMPK/mTOR control into a single regulatory model not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-109582 Hemostasis 3 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2
Partners
DRD3EDN1EDN3RET

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Human EDNRB cDNA was cloned and functionally expressed in COS cells, demonstrating that the receptor binds endothelin isopeptides (ET-1 and ET-3) with approximately equal potency and couples to intracellular Ca2+ transients ([Ca2+]i increases), establishing its non-isopeptide-selective pharmacology. cDNA cloning, radioligand binding (125I-ET-1 displacement), Ca2+ imaging in transfected COS cells Biochemical and biophysical research communications High 1713452
1992 In vivo pharmacological activation of EDNRB with the selective agonist sarafotoxin S6c produces both a transient vasodepressor (endothelium-dependent vasodilation) and a subsequent sustained pressor response with renal and mesenteric vasoconstriction, demonstrating that EDNRB mediates both vasodilation and vasoconstriction in vivo. In vivo pharmacology in rats using selective ETB agonist sarafotoxin S6c; blood pressure and vascular resistance measurements Biochemical and biophysical research communications High 1323294
1993 EDNRB protein localizes to endothelial cells in multiple tissues (kidney, adrenal gland, lung, cerebellum, pituitary gland) as determined by immunohistochemistry using a receptor-specific antiserum that immunoprecipitates only ETB and not ETA; tissue-specific ETB:ETA ratios were quantified (e.g., lung ~70% ETB, testis <2% ETB). Immunohistochemistry, Western blot, and immunoprecipitation with subtype-specific antiserum The American journal of physiology Medium 8476120
1994 Both ETA and ETB receptors mediate contraction in human vascular smooth muscle cells; EDNRB-specific stimulation with sarafotoxin S6c induces contraction in ETA-blocked vessels, and ETB mRNA was detected by Northern blot in smooth muscle cells, establishing that smooth muscle ETB receptors are functionally contractile. Pharmacological antagonism (FR139317, BQ-123, bosentan), sarafotoxin S6c agonism, ETB receptor downregulation by prolonged sarafotoxin S6c preincubation, Northern blot for ETB mRNA Circulation High 8124808
1994 Both ETA and ETB receptors couple to the MAPK cascade (activation of p42 MAPK and MAPKK) and stimulate cell proliferation ([3H]thymidine uptake), as demonstrated in CHO cells transfected with either human ETA or ETB cDNA; ET isopeptide potency differences reflect receptor binding affinities. cDNA transfection of CHO cells, MAPK activity assays, [3H]thymidine incorporation The American journal of physiology High 7943276
1996 ETB receptor activation (by ET-1 in OKPETB6 cells overexpressing EDNRB) stimulates NHE3 (Na+/H+ exchanger isoform 3) activity via tyrosine kinase pathways; ET-1 induces tyrosine phosphorylation of paxillin (68 kDa) and p125FAK via ETB, and this focal adhesion kinase pathway is not required for antiporter activation, whereas a membrane-associated 210 kDa phosphoprotein may mediate 50% of the NHE3 activation. Na+/H+ antiporter activity assays, immunoprecipitation, tyrosine phosphorylation assays, cytochalasin D disruption of focal adhesions in OKP cells overexpressing ETB The American journal of physiology High 8843705
1999 EDNRB activation by ET-1 induces NHE3 phosphorylation on multiple threonine and serine residues in OKP cells expressing ETB receptors (but not ETA receptors); phosphorylation is maximal at 15–30 min with 1 nM ET-1 and correlates temporally and in concentration dependence with NHE3 activation, suggesting phosphorylation mediates ETB-stimulated NHE3 activity. Na+/H+ antiporter activity assays, immunoprecipitation, SDS-PAGE mobility shift, alkaline phosphatase treatment, phosphoamino acid analysis in OKP cells with ETB or ETA receptors The American journal of physiology High 10199826
1999 Genetic and pharmacological disruption of EDNRB in mice elevates arterial blood pressure by ~20 mmHg; this depressor effect of endogenous ET acting through ETB is mediated in part by tonic prostaglandin production (attenuated by indomethacin but not by L-NMMA), not through respiratory control or ET clearance. ETB knockout/hypomorphic mouse model (ETB-/s vs ETB+/s), selective ETB antagonist BQ-788, selective ETA antagonist BQ-123, indomethacin and L-NMMA pharmacology, blood pressure telemetry The American journal of physiology High 10198387
2001 The EDNRB gene 5' CpG island undergoes tissue-specific methylation that silences transcription; low methylation in a small region within the 5' region correlates with expression of the 5'-most transcript, and treatment with 5-aza-2'-deoxycytidine reactivates all four EDNRB transcripts, establishing promoter methylation as a regulatory mechanism. Bisulfite sequencing of 11 individual CpG sites, methylation-sensitive restriction fingerprinting, 5-aza-2'-deoxycytidine demethylation, RT-PCR for transcript expression Human molecular genetics High 11309363
2003 EDNRB activation specifically enhances RET signaling-induced proliferation of uncommitted ENS progenitors; EDNRB and RET signaling have opposing (antagonistic) roles in ENS progenitor migration; protein kinase A (PKA) is a key molecular integrator of EDNRB and RET pathway crosstalk during enteric nervous system development. Primary ENS progenitor culture assays with selective receptor agonists/antagonists, PKA inhibitor/activator pharmacology, proliferation and migration assays Neuron High 14659090
2003 Genetic titration of Ednrb in Ret kinase-null heterozygous mice demonstrates tissue-specific epistasis: EDNRB-RET interaction is restricted to the enteric nervous system and does not affect renal, melanocyte, or retinal choroid development; the degree of Ednrb dosage determines both penetrance and sex bias of aganglionosis. Two-locus noncomplementation assay in mice, allelic series at Ednrb in Ret+/- background, phenotypic analysis of enteric, renal, and coat color phenotypes Proceedings of the National Academy of Sciences of the United States of America High 12574515
2008 Renal medullary EDNRB stimulation (by sarafotoxin S6c infusion) induces diuresis and natriuresis through a NOS1 → cGMP → PKG signaling cascade; S6c-induced increases in urine flow, sodium excretion, and medullary cGMP were absent in ETB receptor-deficient rats and were abolished by selective NOS1 inhibitor or PKG inhibitor. In vivo renal medullary infusion in anesthetized rats, ETB-deficient rat model, selective NOS1 inhibitor (N(G)-propyl-L-arginine), PKG inhibitor, cGMP measurement, urine flow and sodium excretion American journal of physiology. Renal physiology High 18305094
2008 ET-1 impairs alveolar fluid reabsorption via endothelial EDNRB: ETB (not ETA) blockade prevents ET-1-induced decrease in alveolar fluid reabsorption; ET-1 acts on endothelial EDNRB to produce NO (cGMP-independent mechanism) that in turn decreases Na,K-ATPase activity and plasma membrane abundance in alveolar epithelial cells; transgenic rats deficient in pulmonary vascular ETB receptors are protected. Isolated perfused rat lung, ETB-deficient transgenic rats, endothelial-epithelial cell co-culture, ETB/ETA antagonist pharmacology, Na,K-ATPase activity assay, NO synthase inhibitor L-NAME American journal of respiratory and critical care medicine High 18948426
2010 Endothelial cell-specific EDNRB is the primary site responsible for clearance of circulating ET-1; endothelial-specific ETB knockout mice show impaired 125I-ET-1 clearance and elevated plasma ET-1, while ETB binding is selectively decreased in EC-rich tissues (lung, liver, kidney). Endothelial cell-specific Cre-lox ETB knockout mice, 125I-ET-1 clearance assay, autoradiography, immunocytochemistry, RT-PCR, selective ETB antagonist A192621 Canadian journal of physiology and pharmacology High 20628430
2015 After status epilepticus, EDNRB activation drives vasogenic edema by stimulating endothelial eNOS, increasing MMP-9 activity, and degrading the tight junction protein ZO-1 in endothelial cells; ETB antagonist BQ788 attenuates SE-induced vasogenic edema by blocking eNOS-MMP-9-ZO-1 degradation. In vivo rat SE model, ETB antagonist BQ788, immunohistochemistry/immunofluorescence for tight junction proteins, MMP-9 activity assay, eNOS activation assay Neuroscience Medium 26232046
2016 Crystal structure of human EDNRB in ligand-free and ET-1-bound forms reveals that transmembrane helices 1, 2, 6, and 7 move to envelop the entire ET-1 peptide in a virtually irreversible manner; agonist-induced conformational changes propagate to the cytoplasmic G-protein coupling interface and induce flexibility in TM6; mutation analysis defines the mechanism for ET-1 versus ET-3 isopeptide selectivity. X-ray crystallography, site-directed mutagenesis, functional Ca2+ assay Nature High 27595334
2016 EDNRB signaling in melanocyte stem cells promotes their proliferation and differentiation to regenerate hair and epidermal melanocytes; this effect requires active Wnt signaling initiated by Wnt ligand secretion from the hair follicle epithelial niche, and Wnt-dependent EDNRB signaling can rescue defects caused by Mc1R loss. Genetic loss-of-function (EdnrB knockout in melanocyte stem cells), Wnt signaling inhibition/activation, in vivo melanocyte regeneration assays, Mc1R mutant rescue Cell reports High 27134165
2017 Epilation induces endogenous EDN3 upregulation in the dermal papilla, secondary hair germ cells, and epidermis; genetic and pharmacological disruption of EDNRB blocks melanocyte stem cell activation, follicular and epidermal melanocyte regeneration, and skin/hair hyperpigmentation after epilation. In vivo mouse epilation model, EDNRB genetic disruption (conditional knockout), pharmacological EDNRB blockade, immunofluorescence for melanocyte markers Scientific reports High 28779103
2017 EDNRB heterozygous missense mutations cause Waardenburg syndrome type II (pigmentation/hearing loss without Hirschsprung disease) with dominant incomplete penetrance; cellular studies showed that each of six identified mutations impairs subcellular localization of EDNRB or induces defective downstream signaling. Exome sequencing, family segregation analysis, cellular localization studies (immunofluorescence), downstream signaling assays in transfected cells Human mutation Medium 28236341
2017 EDN3-mediated EDNRB signaling prevents premature neuronal differentiation of enteric nervous system progenitor cells; this requires two copies of Zeb2 (ZEB2). SOX10 and ZEB2 directly activate the EDNRB promoter (confirmed by chromatin immunoprecipitation and transactivation assays), and overexpression of EDNRB in Zeb2-heterozygous EPCs restores EDN3-mediated inhibition of differentiation. Enteric progenitor cell cultures, Zeb2 and Edn3 mutant mouse crosses, chromatin immunoprecipitation, transactivation assays, retroviral EDNRB rescue, immunocytochemistry Gastroenterology High 28063956
2018 Crystal structures of human EDNRB bound to ET-3 and the partial agonist IRL1620 reveal that disruption of water-mediated interactions between W6.48 and D2.50 is critical for full receptor activation; IRL1620 partially preserves these hydrogen-bonding interactions, explaining its partial agonism confirmed by functional analysis. X-ray crystallography of ETB-ET3 and ETB-IRL1620 complexes, site-directed mutagenesis, functional Ca2+ signaling assays Nature communications High 30413709
2019 EDNRB transcription in the enteric nervous system is directly regulated by transcription factors GATA2, SOX10, and NKX2.5; RET and EDNRB share GATA2 and SOX10 as regulators, and these TFs are in turn controlled by EDNRB and RET in a dose-dependent feedback manner, explaining RET-EDNRB epistasis in Hirschsprung disease. Human and mouse cellular models, ChIP assays, reporter gene assays, animal models of EDNRB and RET expression Human molecular genetics High 31313802
2009 D3 dopamine receptors physically interact with EDNRB (co-immunoprecipitation) in renal proximal tubule cells; D3 receptor activation increases ETB receptor expression (calcium-dependent, blocked by nicardipine) in WKY rats and augments ETB-mediated inhibition of Na+/K+-ATPase activity; this D3-ETB interaction is impaired in spontaneously hypertensive rats. Co-immunoprecipitation, immunoblotting, RT-PCR, Na+/K+-ATPase activity assay, selective agonist/antagonist pharmacology American journal of hypertension Medium 19390510
2008 ETB receptor activation mediates apoptosis of retinal ganglion cells (RGC-5 cells) via cytochrome c release from mitochondria and JNK phosphorylation; ET-1-induced apoptosis was markedly attenuated in ETB receptor-deficient rats and by ETB antagonist BQ788 in cultured cells. Flow cytometry, cytochrome c release assay, JNK phosphorylation assay, ETB-deficient rat model, BQ788 pharmacology Canadian journal of physiology and pharmacology Medium 18516102
1997 A critical proline residue in the fifth transmembrane domain of EDNRB is required for function in vivo (Ednrb27Pub allele); loss of authentic Ednrb mRNA (Ednrb3Chlo allele, gross genomic deletion) or reduced mRNA level (Ednrb17FrS) causes juvenile lethality and pigmentation defects, demonstrating that EDNRB expression level is dosage-sensitive for melanocyte development. Molecular characterization of four ENU/radiation-induced mouse Ednrb alleles by sequencing, mRNA analysis (Northern blot/RT-PCR), and phenotypic analysis Proceedings of the National Academy of Sciences of the United States of America High 9371807
2018 miR-124-3p directly targets EDNRB (confirmed by dual-luciferase reporter assay); miR-124-3p suppresses EDNRB expression and thereby inhibits bladder cancer cell proliferation and induces apoptosis; EDNRB siRNA phenocopies miR-124-3p mimic effects. Dual-luciferase reporter assay, qRT-PCR, Western blot, siRNA knockdown, cell proliferation (MTS/colony assay), flow cytometry apoptosis assay, nude mouse tumorigenicity assay Archives of medical science Medium 31572460
2018 Homocysteine upregulates EDNRB in vascular smooth muscle cells by inhibiting autophagy via the AMPK/mTOR signaling pathway; AMPK activator (AICAR) or mTOR inhibitor (rapamycin) reverses Hcy-induced ETB receptor upregulation and contractile responses, while mTOR activator (MHY1485) restores the effect. Rat superior mesenteric artery myograph, Western blot, immunofluorescence for LC3B (autophagy marker), AICAR/rapamycin/MHY1485 pharmacology Microvascular research Medium 29601873

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation 473 8124808
1992 The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochemical and biophysical research communications 395 1323294
1991 Cloning and functional expression of human cDNA for the ETB endothelin receptor. Biochemical and biophysical research communications 272 1713452
1992 A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor. Biochemical and biophysical research communications 258 1315540
1995 Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation 256 7634449
2007 Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annual review of pharmacology and toxicology 243 17002597
2003 Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron 213 14659090
1996 Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease. Human molecular genetics 174 8852660
1999 Endothelin-1 potentiates human smooth muscle cell growth to PDGF: effects of ETA and ETB receptor blockade. Circulation 136 10393673
2016 Activation mechanism of endothelin ETB receptor by endothelin-1. Nature 128 27595334
2003 Phenotype variation in two-locus mouse models of Hirschsprung disease: tissue-specific interaction between Ret and Ednrb. Proceedings of the National Academy of Sciences of the United States of America 119 12574515
1994 Endothelin ETA- and ETB-receptor-mediated vasoconstriction in rat pulmonary arteries and arterioles. Journal of cardiovascular pharmacology 112 7521470
2006 Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development. Developmental biology 105 16650841
2004 Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease. Human molecular genetics 93 15294878
2001 The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells. Human molecular genetics 88 11309363
2010 KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses. International journal of cancer 80 20162572
2001 EDNRB/EDN3 and Hirschsprung disease type II. Pigment cell research 80 11434563
1999 Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of endothelin-1 in failing rat heart. The American journal of physiology 80 10199843
2005 ETA and ETB receptors differentially modulate afferent and efferent arteriolar responses to endothelin. British journal of pharmacology 77 16231007
1999 ETB receptor activation leads to activation and phosphorylation of NHE3. The American journal of physiology 77 10199826
2013 EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions. Clinical cancer research : an official journal of the American Association for Cancer Research 76 23637120
2006 Distribution of endothelin receptor subtypes ETA and ETB in the rat kidney. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 76 16835394
2016 EdnrB Governs Regenerative Response of Melanocyte Stem Cells by Crosstalk with Wnt Signaling. Cell reports 72 27134165
2005 Evaluation of the RET regulatory landscape reveals the biological relevance of a HSCR-implicated enhancer. Human molecular genetics 67 16269442
2002 Gender differences in ET and NOS systems in ETB receptor-deficient rats: effect of a high salt diet. Hypertension (Dallas, Tex. : 1979) 67 12623975
2018 Crystal structures of human ETB receptor provide mechanistic insight into receptor activation and partial activation. Nature communications 65 30413709
1999 Elevation of blood pressure by genetic and pharmacological disruption of the ETB receptor in mice. The American journal of physiology 65 10198387
2008 Renal medullary ETB receptors produce diuresis and natriuresis via NOS1. American journal of physiology. Renal physiology 64 18305094
2003 Functional haplotypes of the RET proto-oncogene promoter are associated with Hirschsprung disease (HSCR). Human molecular genetics 63 14600022
2018 News from the endothelin-3/EDNRB signaling pathway: Role during enteric nervous system development and involvement in neural crest-associated disorders. Developmental biology 62 30171849
1993 Immunochemical characterization and localization of endothelin ETB receptor. The American journal of physiology 56 8476120
2010 Endothelial cell-specific ETB receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1. Canadian journal of physiology and pharmacology 55 20628430
2007 Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage. American journal of physiology. Heart and circulatory physiology 55 17873013
2001 Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease. Gut 55 11302967
2008 Role of the ETB receptor in retinal ganglion cell death in glaucoma. Canadian journal of physiology and pharmacology 54 18516102
2002 Promoter hypermethylation of the EDNRB gene in nasopharyngeal carcinoma. International journal of cancer 54 11920632
1996 Role of tyrosine kinase pathways in ETB receptor activation of NHE3. The American journal of physiology 54 8843705
2013 Hypermethylation of EDNRB promoter contributes to the risk of colorectal cancer. Diagnostic pathology 51 24326135
2006 MEK1/2 inhibition attenuates vascular ETA and ETB receptor alterations after cerebral ischaemia. Experimental brain research 50 17091294
2015 ETB receptor-mediated MMP-9 activation induces vasogenic edema via ZO-1 protein degradation following status epilepticus. Neuroscience 49 26232046
2013 Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease. Neurogastroenterology and motility 46 23360229
2011 Re-expression of the methylated EDNRB gene in oral squamous cell carcinoma attenuates cancer-induced pain. Pain 46 21782343
2010 New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. Genetics in medicine : official journal of the American College of Medical Genetics 44 20009762
1996 Localization of endothelin ETA and ETB receptor-mediated constriction in the renal microcirculation of rats. The Journal of physiology 44 8951723
2017 ETB receptor contribution to vascular dysfunction in postmenopausal women. American journal of physiology. Regulatory, integrative and comparative physiology 43 28438762
2012 Genome-wide copy number analysis uncovers a new HSCR gene: NRG3. PLoS genetics 43 22589734
2010 Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations. Nature structural & molecular biology 41 20473317
1995 Functional role of endothelin ETA and ETB receptors in venous and arterial smooth muscle. European journal of pharmacology 41 8991802
2006 Aberrant methylation of EDNRB and p16 genes in hepatocellular carcinoma (HCC) in Taiwan. Oncology reports 39 16391877
2005 Delphinidin-3-rutinoside relaxes the bovine ciliary smooth muscle through activation of ETB receptor and NO/cGMP pathway. Experimental eye research 39 15721614
2018 The effect of miR-124-3p on cell proliferation and apoptosis in bladder cancer by targeting EDNRB. Archives of medical science : AMS 38 31572460
2002 BQ-788, a selective endothelin ET(B) receptor antagonist. Cardiovascular drug reviews 38 12070534
1995 ETB and epidermal growth factor receptor stimulation of wound closure in bovine corneal epithelial cells. Investigative ophthalmology & visual science 38 7499084
2008 Endothelin-1 impairs alveolar epithelial function via endothelial ETB receptor. American journal of respiratory and critical care medicine 37 18948426
2004 Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline-induced pulmonary hypertension. Journal of cardiovascular pharmacology 37 15243299
1994 Endothelins stimulate mitogen-activated protein kinase cascade through either ETA or ETB. The American journal of physiology 37 7943276
2006 Expression and immunolocalization of endothelin peptides and its receptors, ETA and ETB, in the carotid body exposed to chronic intermittent hypoxia. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 36 17046837
1996 Decreased ET(B) receptor expression in human metastatic melanoma cells. Biochemical and biophysical research communications 36 8645250
2017 EDNRB mutations cause Waardenburg syndrome type II in the heterozygous state. Human mutation 35 28236341
2008 ADP-ribosyl cyclase and ryanodine receptors mediate endothelin ETA and ETB receptor-induced renal vasoconstriction in vivo. American journal of physiology. Renal physiology 35 18524860
2003 ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury. American journal of physiology. Gastrointestinal and liver physiology 35 12799311
2011 Quantitative analysis of promoter methylation of the EDNRB gene in gastric cancer. Medical oncology (Northwood, London, England) 34 21264540
2017 Epilation induces hair and skin pigmentation through an EDN3/EDNRB-dependent regenerative response of melanocyte stem cells. Scientific reports 33 28779103
2008 Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertension. Canadian journal of physiology and pharmacology 33 18758497
2003 ACE inhibition increases expression of the ETB receptor in kidneys of mice with unilateral obstruction. American journal of physiology. Renal physiology 33 12473537
2002 ABCD syndrome is caused by a homozygous mutation in the EDNRB gene. American journal of medical genetics 32 11891690
1994 Divergent expression of EtA and EtB receptors in response to cyclosporine in mesangial cells. The American journal of pathology 31 8129032
2009 D3 dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRs. American journal of hypertension 30 19390510
2021 Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders. International journal of molecular sciences 29 33919338
2017 Differentiation of Mouse Enteric Nervous System Progenitor Cells Is Controlled by Endothelin 3 and Requires Regulation of Ednrb by SOX10 and ZEB2. Gastroenterology 29 28063956
2022 BACE2 variant identified from HSCR patient causes AD-like phenotypes in hPSC-derived brain organoids. Cell death discovery 28 35110536
2019 A gene regulatory network explains RET-EDNRB epistasis in Hirschsprung disease. Human molecular genetics 28 31313802
2019 Endothelin-1 increases expression and activity of arginase 2 via ETB receptors and is co-expressed with arginase 2 in human atherosclerotic plaques. Atherosclerosis 28 31606133
2017 Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal mucosa of obese rats, are downregulated by three probiotic strains. Scientific reports 28 28512356
2004 ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor-deficient rats. Journal of cardiovascular pharmacology 28 15838363
2003 Unique endothelin receptor binding in kidneys of ETB receptor deficient rats. American journal of physiology. Regulatory, integrative and comparative physiology 28 12611392
1994 Effects of selective ETB-receptor stimulation on arterial, venous and capillary functions in cat skeletal muscle. British journal of pharmacology 28 7921617
2012 Comparison of human ETA and ETB receptor signalling via G-protein and β-arrestin pathways. Life sciences 27 22480514
1995 Identification and function of putative ETB receptor subtypes in the dog kidney. Journal of cardiovascular pharmacology 26 8587403
2017 LncRNA AFAP1-AS Functions as a Competing Endogenous RNA to Regulate RAP1B Expression by sponging miR-181a in the HSCR. International journal of medical sciences 25 28924375
2004 Role of endothelin ETB receptor in the pathogenesis of monocrotaline-induced pulmonary hypertension in rats. European journal of pharmacology 25 15359489
2021 ETB receptor-mediated vasodilation is regulated by estradiol in young women. American journal of physiology. Heart and circulatory physiology 24 34415188
2008 Identification of aberrant promoter methylation of EDNRB gene in esophageal squamous cell carcinoma. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 24 18564167
2004 Inotropic effects of ETB receptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins. American journal of physiology. Heart and circulatory physiology 24 15130886
2020 Role of endothelin receptor type B (EDNRB) in lung adenocarcinoma. Thoracic cancer 23 32394530
2013 Methylation analysis of EDNRB in human colon tissues of Hirschsprung's disease. Pediatric surgery international 23 23579558
2011 Expression of PROKR1 and PROKR2 in human enteric neural precursor cells and identification of sequence variants suggest a role in HSCR. PloS one 23 21858136
2020 Altered endothelial ETB receptor expression in postmenopausal women. American journal of physiology. Heart and circulatory physiology 21 32559137
2019 Endothelins (EDN1, EDN2, EDN3) and their receptors (EDNRA, EDNRB, EDNRB2) in chickens: Functional analysis and tissue distribution. General and comparative endocrinology 21 31351053
2007 Protein kinase C inhibition attenuates vascular ETB receptor upregulation and decreases brain damage after cerebral ischemia in rat. BMC neuroscience 21 17212812
2017 TRPC3- and ETB receptor-mediated PI3K/AKT activation induces vasogenic edema formation following status epilepticus. Brain research 20 28764936
2014 Effect of SNP polymorphisms of EDN1, EDNRA, and EDNRB gene on ischemic stroke. Cell biochemistry and biophysics 20 24633486
1997 Identification and characterization of a novel endothelin receptor that binds both ETA- and ETB-selective ligands. Molecular pharmacology 20 9380020
2018 Homocysteine up-regulates ETB receptors via suppression of autophagy in vascular smooth muscle cells. Microvascular research 19 29601873
2008 Expression and function of ETA and ETB receptors in SSc. Rheumatology (Oxford, England) 19 18784135
1997 Molecular characterization of four induced alleles at the Ednrb locus. Proceedings of the National Academy of Sciences of the United States of America 19 9371807
2013 Valproic acid substantially downregulated genes folr1, IGF2R, RGS2, COL6A3, EDNRB, KLF6, and pax-3, N-acetylcysteine alleviated most of the induced gene alterations in chicken embryo model. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 18 24398995
2008 Epigenetic and genetic alterations of the EDNRB gene in nasopharyngeal carcinoma. Oncology 18 18187958
2006 Aberrant promoter methylation of EDNRB in lung cancer in Taiwan. Oncology reports 18 16328051
2005 Low RET mutation frequency and polymorphism analysis of the RET and EDNRB genes in patients with Hirschsprung disease in Taiwan. Journal of human genetics 18 15834508

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