endothelin b receptor


Summary: A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.

Top Publications

  1. Tian J, Wong W, Tian X, Zhang P, Huang Y, Wang N. Rosiglitazone attenuates endothelin-1-induced vasoconstriction by upregulating endothelial expression of endothelin B receptor. Hypertension. 2010;56:129-35 pubmed publisher
    ..In conclusion, these results demonstrate that rosiglitazone attenuated ET-1-induced vasoconstriction through the upregulation of endothelial ET(B)R, which is a peroxisome proliferator-activated receptor-gamma direct target. ..
  2. He S, Dibas A, Yorio T, Prasanna G. Parallel signaling pathways in endothelin-1-induced proliferation of U373MG astrocytoma cells. Exp Biol Med (Maywood). 2007;232:370-84 pubmed
    ..There is no apparent, direct "cross talk" between these pathways in U373MG cells, but rather, they might act on the independent but necessary components of the mitogenic effects of ET-1. ..
  3. Binder C, Hagemann T, Sperling S, Schulz M, Pukrop T, Grimshaw M, et al. Stromal endothelin B receptor-deficiency inhibits breast cancer growth and metastasis. Mol Cancer Ther. 2009;8:2452-60 pubmed publisher
    ..This shows that tumor growth and metastasis are critically dependent on ET(B)R function in cells of the microenvironment and suggests that successful ETR antagonist therapy should also target the stromal component of ET signaling..
  4. Spinella F, Rosanò L, Di Castro V, Decandia S, Nicotra M, Natali P, et al. Endothelin-1 and endothelin-3 promote invasive behavior via hypoxia-inducible factor-1alpha in human melanoma cells. Cancer Res. 2007;67:1725-34 pubmed
    ..New therapeutic strategies using specific ET(B)R antagonist could provide an improved approach to the treatment of melanoma by inhibiting tumor growth and progression. ..
  5. Guo X, Yang T. Endothelin B receptor antagonism in the rat renal medulla reduces urine flow rate and sodium excretion. Exp Biol Med (Maywood). 2006;231:1001-5 pubmed
  6. Beg S, Hansen Schwartz J, Vikman P, Xu C, Edvinsson L. ERK1/2 inhibition attenuates cerebral blood flow reduction and abolishes ET(B) and 5-HT(1B) receptor upregulation after subarachnoid hemorrhage in rat. J Cereb Blood Flow Metab. 2006;26:846-56 pubmed
    ..The results suggest that ERK1/2 inhibition might be a potential treatment for the prevention of cerebral vasospasm and ischemia associated with SAH. ..
  7. Klammt C, Srivastava A, Eifler N, Junge F, Beyermann M, Schwarz D, et al. Functional analysis of cell-free-produced human endothelin B receptor reveals transmembrane segment 1 as an essential area for ET-1 binding and homodimer formation. FEBS J. 2007;274:3257-69 pubmed
    ..Human endothelin B receptor was cell-free produced as a precipitate and subsequently solubilized in detergent, or was directly ..
  8. He G, Liu M, Yang Q, Furnary A, Yim A. Role of endothelin-1 receptor antagonists in vasoconstriction mediated by endothelin and other vasoconstrictors in human internal mammary artery. Ann Thorac Surg. 2007;84:1522-7 pubmed
    ..We studied the role of antagonists for both ET(A) and ET(B) receptors in vasoconstriction mediated by endothelin-1 and other vasoconstrictors in the human internal mammary artery (IMA)...
  9. Pfab T, Thone Reineke C, Theilig F, Lange I, Witt H, Maser Gluth C, et al. Diabetic endothelin B receptor-deficient rats develop severe hypertension and progressive renal failure. J Am Soc Nephrol. 2006;17:1082-9 pubmed
    ..The study demonstrates for the first time that the combination of diabetes and ETBR deficiency causes severe low-renin hypertension with progressive renal failure...

More Information


  1. Henriksson M, Stenman E, Vikman P, Edvinsson L. MEK1/2 inhibition attenuates vascular ETA and ETB receptor alterations after cerebral ischaemia. Exp Brain Res. 2007;178:470-6 pubmed
    ..The vascular effects of U0126 provide new perspective on possible mechanisms of actions of MAPK inhibition in cerebral ischaemia. ..
  2. Ansar S, Vikman P, Nielsen M, Edvinsson L. Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage. Am J Physiol Heart Circ Physiol. 2007;293:H3750-8 pubmed
    ..These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage. ..
  3. Buckanovich R, Facciabene A, Kim S, Benencia F, Sasaroli D, Balint K, et al. Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat Med. 2008;14:28-36 pubmed
    ..Overexpression of the endothelin B receptor (ET(B)R) was associated with the absence of TILs and short patient survival time...
  4. Granström B, Xu C, Nilsson E, Vikman P, Edvinsson L. Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi. BMC Pulm Med. 2006;6:6 pubmed
    ..Taken as a whole, this is seen as the presence of a translation mechanism. The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism. ..
  5. Wang X, LeVatte T, Archibald M, Chauhan B. Increase in endothelin B receptor expression in optic nerve astrocytes in endothelin-1 induced chronic experimental optic neuropathy. Exp Eye Res. 2009;88:378-85 pubmed publisher
    ..There was a weak relationship between RGC loss and increase in ETB expression (r = -0.417, p = 0.076). There is an upregulation of ETB expression in optic nerve astrocytes in ET-1 induced chronic optic neuropathy causing RGC loss. ..
  6. Nilsson D, Wackenfors A, Gustafsson L, Ugander M, Ingemansson R, Edvinsson L, et al. PKC and MAPK signalling pathways regulate vascular endothelin receptor expression. Eur J Pharmacol. 2008;580:190-200 pubmed
    ..Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin receptor changes in cardiovascular disease. ..
  7. Nilsson D, Wackenfors A, Gustafsson L, Edvinsson L, Paulsson P, Ingemansson R, et al. Increased ET(A) and ET(B) receptor contraction in the left internal mammary artery from patients with hypertension. J Hum Hypertens. 2008;22:226-9 pubmed
  8. Tang L, Luo B, Patel R, Ling Y, Zhang J, Fallon M. Modulation of pulmonary endothelial endothelin B receptor expression and signaling: implications for experimental hepatopulmonary syndrome. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1467-72 pubmed
    ..These findings support that increased pulmonary microvascular endothelial ET(B) receptor expression modulates ET-1-mediated eNOS activation, independent of Akt, and contributes to the development of HPS. ..
  9. Nilsson D, Wackenfors A, Gustafsson L, Ugander M, Paulsson P, Ingemansson R, et al. Endothelin receptor-mediated vasodilatation: effects of organ culture. Eur J Pharmacol. 2008;579:233-40 pubmed
    ..Down-regulation of endothelial endothelin ET(B) receptors may in part explain the increased endothelin ET(B) receptor-mediated vasoconstriction frequently studied in organ culture. ..
  10. Konczalla J, Vatter H, Weidauer S, Raabe A, Seifert V. Alteration of the cerebrovascular function of endothelin B receptor after subarachnoidal hemorrhage in the rat. Exp Biol Med (Maywood). 2006;231:1064-8 pubmed
    ..The present data indicate the loss of the ET(B) receptor-mediated relaxation of the cerebral arteries in cases of CVS, which is independent of the endothelial nitric oxide synthase level. ..
  11. Sullivan J, Pollock J, Pollock D. Superoxide-dependent hypertension in male and female endothelin B receptor-deficient rats. Exp Biol Med (Maywood). 2006;231:818-23 pubmed
  12. Schneider M, Boesen E, Pollock D. Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annu Rev Pharmacol Toxicol. 2007;47:731-59 pubmed
    ..Considerable questions remain regarding whether ET(A)-selective or nonselective ET(A)/ET(B) receptor antagonists would be useful in a range of clinical settings. ..
  13. Patel N, Gonsalves C, Malik P, Kalra V. Placenta growth factor augments endothelin-1 and endothelin-B receptor expression via hypoxia-inducible factor-1 alpha. Blood. 2008;112:856-65 pubmed publisher
    ..PlGF levels are intrinsically elevated from the increased red cell turnover in SCD and in other chronic anemia (eg, thalassemia) and may contribute to inflammation and PHT seen in these diseases. ..
  14. Luo G, Jamali R, Cao Y, Edvinsson L, Xu C. Vascular endothelin ET(B) receptor-mediated contraction requires phosphorylation of ERK1/2 proteins. Eur J Pharmacol. 2006;538:124-31 pubmed
    ..Thus, phosphorylation of ERK1/2 proteins and elevation of intracellular calcium level are required for endothelin ET(B) receptor-mediated contraction in rat mesenteric artery. ..
  15. Ge Y, Bagnall A, Stricklett P, Strait K, Webb D, Kotelevtsev Y, et al. Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am J Physiol Renal Physiol. 2006;291:F1274-80 pubmed
    ..CD ETA and ETB receptors do not fully account for the antihypertensive and natriuretic effects of CD-derived ET-1, suggesting paracrine effects of this peptide. ..
  16. Foller M, Mahmud H, Qadri S, Gu S, Braun M, Bobbala D, et al. Endothelin B receptor stimulation inhibits suicidal erythrocyte death. FASEB J. 2010;24:3351-9 pubmed publisher
    ..The observations disclose a novel function of ET1, i.e., protection from suicidal erythrocyte death. ..
  17. Nilsson D, Gustafsson L, Wackenfors A, Gesslein B, Edvinsson L, Paulsson P, et al. Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways. BMC Cardiovasc Disord. 2008;8:21 pubmed publisher
    ..Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ETB receptor changes in cardiovascular disease. ..
  18. Alken M, Schmidt A, Rutz C, Furkert J, Kleinau G, Rosenthal W, et al. The sequence after the signal peptide of the G protein-coupled endothelin B receptor is required for efficient translocon gating at the endoplasmic reticulum membrane. Mol Pharmacol. 2009;75:801-11 pubmed publisher
    ..Taking the endothelin B receptor as a model, we describe a new type of a transport-relevant GPCR domain...
  19. Henriksson M, Vikman P, Stenman E, Beg S, Edvinsson L. Inhibition of PKC activity blocks the increase of ETB receptor expression in cerebral arteries. BMC Pharmacol. 2006;6:13 pubmed
    ..Since ETB receptor upregulation is seen in cerebral ischemia, the results of the present study provide a way to interfere with the vascular involvement in cerebral ischemia. ..
  20. Ling Y, Zhang J, Luo B, Song D, Liu L, Tang L, et al. The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat. Hepatology. 2004;39:1593-602 pubmed
    ..Selective ET(B) receptor blockade also decreased macrophage accumulation and iNOS production. In conclusion, ET-1 plays a central role in modulating pulmonary micovascular tone in experimental HPS. ..
  21. Henriksson M, Stenman E, Edvinsson L. Intracellular pathways involved in upregulation of vascular endothelin type B receptors in cerebral arteries of the rat. Stroke. 2003;34:1479-83 pubmed
    ..This upregulation is due to de novo transcription of receptors. Protein kinase C is involved in the upregulation as Ro-31-8220 attenuates the contraction and the mRNA increase. ..
  22. Watabe H, Soma Y, Kawa Y, Ito M, Ooka S, Ohsumi K, et al. Differentiation of murine melanocyte precursors induced by 1,25-dihydroxyvitamin D3 is associated with the stimulation of endothelin B receptor expression. J Invest Dermatol. 2002;119:583-9 pubmed
    ..Moreover, immunostaining and reverse transcription-polymerase chain reaction analysis revealed that endothelin B receptor expression was induced in NCC-/melb4 cells following treatment with 1,25-dihydroxyvitamin D3...
  23. Bagnato A, Spinella F. Emerging role of endothelin-1 in tumor angiogenesis. Trends Endocrinol Metab. 2003;14:44-50 pubmed
  24. Hou L, Pavan W, Shin M, Arnheiter H. Cell-autonomous and cell non-autonomous signaling through endothelin receptor B during melanocyte development. Development. 2004;131:3239-47 pubmed
    ..The results suggest that Ednrb plays a significant role during melanocyte differentiation and effects melanocyte development by both cell non-autonomous and cell-autonomous signaling mechanisms. ..
  25. Granström B, Xu C, Nilsson E, Bengtsson U, Edvinsson L. Up-regulation of endothelin receptor function and mRNA expression in airway smooth muscle cells following Sephadex-induced airway inflammation. Basic Clin Pharmacol Toxicol. 2004;95:43-8 pubmed
  26. Just A, Olson A, Arendshorst W. Dual constrictor and dilator actions of ET(B) receptors in the rat renal microcirculation: interactions with ET(A) receptors. Am J Physiol Renal Physiol. 2004;286:F660-8 pubmed
    ..Possible explanations include ET-1 clearance by ET(B) receptors and/or a dilator ET(B) receptor function that counteracts constriction. ..
  27. Hansen Schwartz J, Svensson C, Xu C, Edvinsson L. Protein kinase mediated upregulation of endothelin A, endothelin B and 5-hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery. Br J Pharmacol. 2002;137:118-26 pubmed
    ..This lack of correlation indicates an additional downstream involvement of protein kinases. ..
  28. Luo B, Liu L, Tang L, Zhang J, Stockard C, Grizzle W, et al. Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome. J Hepatol. 2003;38:556-63 pubmed
    ..in pre-hepatic portal hypertension after portal vein ligation (PVL) initiate vasodilatation through an endothelin B receptor mediated increase in pulmonary endothelial nitric oxide synthase (eNOS)...
  29. Harada N, Himeno A, Shigematsu K, Sumikawa K, Niwa M. Endothelin-1 binding to endothelin receptors in the rat anterior pituitary gland: possible formation of an ETA-ETB receptor heterodimer. Cell Mol Neurobiol. 2002;22:207-26 pubmed
    ..If this thesis is tenable, then ET-1 can bridge between the two receptors to form an ETA-ETB receptor heterodimer. ..
  30. Wu Wong J, Dixon D, Chiou W, Sorensen B, Liu G, Jae H, et al. Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: in vitro studies. Clin Sci (Lond). 2002;103 Suppl 48:107S-111S pubmed
  31. Henriksson M, Xu C, Edvinsson L. Importance of ERK1/2 in upregulation of endothelin type B receptors in cerebral arteries. Br J Pharmacol. 2004;142:1155-61 pubmed
    ..Since there is a similar upregulation in models of focal ischaemia and subarachnoid haemorrhage, this may be an important pathophysiological event. ..
  32. Grimshaw M, Hagemann T, Ayhan A, Gillett C, Binder C, Balkwill F. A role for endothelin-2 and its receptors in breast tumor cell invasion. Cancer Res. 2004;64:2461-8 pubmed
    ..We suggest that expression of ETs and their receptors by human breast tumors, particularly in conjunction with a high macrophage infiltrate, may have a role in the progression of breast cancer and the invasion of tumor cells. ..
  33. Wackenfors A, Ingemansson R, Malmsjo M. Endothelin receptors in endothelium-denuded human coronary artery bypass grafts and coronary arteries. Ann Thorac Surg. 2003;75:874-81 pubmed
    ..The lower levels of ET(A) and ET(B) receptor mRNA in the LIMA and coronary arteries as compared with in the SV may provide one explanation for the better long- and short-term patency of LIMA as compared with SV grafts. ..
  34. Uddman E, Adner M, Edvinsson L. Protein kinase C inhibitors decrease endothelin ET(B) receptor mRNA expression and contraction during organ culture of rat mesenteric artery. Eur J Pharmacol. 2002;452:215-22 pubmed
    ..These results suggest that PKC is involved in the endothelin ET(B) receptor upregulation following organ culture. ..
  35. Stenman E, Malmsjo M, Uddman E, Gido G, Wieloch T, Edvinsson L. Cerebral ischemia upregulates vascular endothelin ET(B) receptors in rat. Stroke. 2002;33:2311-6 pubmed
    ..These results suggest a role for ET receptors in the pathogenesis of a vascular component after cerebral ischemia. ..
  36. Wülfing P, Diallo R, Kersting C, Wulfing C, Poremba C, Rody A, et al. Expression of endothelin-1, endothelin-A, and endothelin-B receptor in human breast cancer and correlation with long-term follow-up. Clin Cancer Res. 2003;9:4125-31 pubmed
    ..Therefore, analysis of ET(A)R expression may improve the prediction of relapse and death and facilitate an individually based risk-directed adjuvant therapy in breast cancer patients. ..
  37. Eibl G, Forgacs B, Hotz H, Buhr H, Foitzik T. Endothelin A but not endothelin B receptor blockade reduces capillary permeability in severe experimental pancreatitis. Pancreas. 2002;25:e15-20 pubmed
    ..This may explain the inconclusive results reported with nonselective ET-RA. In severe AP, blockade of ET-A but not ET-B receptors reduces CapPerm. ..
  38. Williams J, Zhao X, Wang M, Imig J, Pollock D. Peroxisome proliferator-activated receptor-alpha activation reduces salt-dependent hypertension during chronic endothelin B receptor blockade. Hypertension. 2005;46:366-71 pubmed
    ..This suggests a possible relationship between ETB receptor activation and the maintenance of CYP4A protein expression in the kidney of rats fed a high-salt diet. ..
  39. Wackenfors A, Emilson M, Ingemansson R, Hortobagyi T, Szok D, Tajti J, et al. Ischemic heart disease induces upregulation of endothelin receptor mRNA in human coronary arteries. Eur J Pharmacol. 2004;484:103-9 pubmed
    ..Increased endothelin receptor activity may contribute to the increased vascular tone and development of atherosclerotic disease in ischemic heart disease in man. ..
  40. Gregan B, Jürgensen J, Papsdorf G, Furkert J, Schaefer M, Beyermann M, et al. Ligand-dependent differences in the internalization of endothelin A and endothelin B receptor heterodimers. J Biol Chem. 2004;279:27679-87 pubmed
    ..Heterodimer dissociation along the endocytic pathway only occurs upon ET(B)-selective stimulation. ..
  41. Landry J, Mager D. Functional analysis of the endogenous retroviral promoter of the human endothelin B receptor gene. J Virol. 2003;77:7459-66 pubmed
    ..belonging to the HERV-E family contribute to the expression of the human apolipoprotein C1 (APOC1) and endothelin B receptor (EDNRB) genes by providing alternative promoters...
  42. Chuquet J, Benchenane K, Toutain J, Mackenzie E, Roussel S, Touzani O. Selective blockade of endothelin-B receptors exacerbates ischemic brain damage in the rat. Stroke. 2002;33:3019-25 pubmed
  43. Lahav R, Suva M, Rimoldi D, Patterson P, Stamenkovic I. Endothelin receptor B inhibition triggers apoptosis and enhances angiogenesis in melanomas. Cancer Res. 2004;64:8945-53 pubmed
  44. Takahashi K, Totsune K, Kitamuro T, Sone M, Murakami O, Shibahara S. Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin: expression and effects on proliferation. Clin Sci (Lond). 2002;103 Suppl 48:35S-38S pubmed
    ..These results suggest that endothelin-1 acts as a paracrine or autocrine growth stimulator in tumours. The effect of endothelin-1 on tumour growth appears to be mediated by the ET(A) receptor. ..
  45. Naidoo V, Naidoo S, Mahabeer R, Raidoo D. Localization of the endothelin system in human diffuse astrocytomas. Cancer. 2005;104:1049-57 pubmed
    ..The mitogenic and antiapoptotic properties of ET-1, as well as the vasodilatory signaling of ETB receptors, may promote tumorigenesis. ..
  46. Zhang Y, Adner M, Cardell L. Interleukin-1beta attenuates endothelin B receptor-mediated airway contractions in a murine in vitro model of asthma: roles of endothelin converting enzyme and mitogen-activated protein kinase pathways. Clin Exp Allergy. 2004;34:1480-7 pubmed
    ..Presence of IL-1beta in the airways attenuate the contractile response mediated via ETB receptors, an effect dependent on ECE, JNK and ERK 1/2 pathways. ..
  47. Bagnato A, Rosanò L, Spinella F, Di Castro V, Tecce R, Natali P. Endothelin B receptor blockade inhibits dynamics of cell interactions and communications in melanoma cell progression. Cancer Res. 2004;64:1436-43 pubmed
    Phenotypic and genotypic analyses of cutaneous melanoma have identified the endothelin B receptor (ET(B)R) as tumor progression marker, thus representing a potential therapeutic target...
  48. Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T. Regulated interaction of endothelin B receptor with caveolin-1. Eur J Biochem. 2003;270:1816-27 pubmed
    ..The disruption of caveolae by filipin reduced the ET-1-derived phosphorylation of ERK1/2. These results suggest the possibility that the binding to caveolin-1 retains the ligand-free ETBR in caveolae and regulates the ET signal. ..
  49. Eberle J, Fecker L, Orfanos C, Geilen C. Endothelin-1 decreases basic apoptotic rates in human melanoma cell lines. J Invest Dermatol. 2002;119:549-55 pubmed
    ..This antiapoptotic activity of endothelin for melanoma cells combined with upregulation of endothelin receptors in the tumor may be a crucial step for melanoma progression. ..
  50. Uddman E, Henriksson M, Eskesen K, Edvinsson L. Role of mitogen-activated protein kinases in endothelin ETB receptor up-regulation after organ culture of rat mesenteric artery. Eur J Pharmacol. 2003;482:39-47 pubmed
    ..Neither Western blot nor myograph or mRNA analysis showed involvement of the other MAPKs studied. Our results suggest that the ERK1/2 MAPKs are involved in the endothelin ET(B) receptor up-regulation following organ culture. ..
  51. Rai A, Gulati A. Evidence for the involvement of ET(B) receptors in ET-1-induced changes in blood flow to the rat breast tumor. Cancer Chemother Pharmacol. 2003;51:21-8 pubmed
    ..The results indicate that ET-1 induced an increase in blood flow to breast tumor tissue mediated through ET(B) receptors. ..
  52. Lahav R. Endothelin receptor B is required for the expansion of melanocyte precursors and malignant melanoma. Int J Dev Biol. 2005;49:173-80 pubmed
  53. Tanoue A, Koshimizu T, Tsuchiya M, Ishii K, Osawa M, Saeki M, et al. Two novel transcripts for human endothelin B receptor produced by RNA editing/alternative splicing from a single gene. J Biol Chem. 2002;277:33205-12 pubmed
    Hirschsprung disease is a heterogeneous genetic disorder, causative genes of which include the endothelin B receptor (ETB)...