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Gene Review

ETBR  -  endothelin B receptor

Ovis aries

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Disease relevance of ETBR


High impact information on ETBR

  • Plasma endothelin-1 and cGMP levels and lung NOS activity, cGMP, eNOS, preproendothelin-1, endothelin-converting enzyme-1, endothelin A, and endothelin B receptor protein levels were similar in both groups [2].
  • Ligation of the ductus arteriosus was also associated with increased expression of preproendothelin-1 mRNA and with decreased expression of endothelin B receptor (ET(B)) mRNA [3].
  • 3. As expected, sheep isolated tracheal smooth muscle preparations did not contract in response to the ETB receptor-selective agonist, sarafotoxin S6c (0.1-100 nM) [4].
  • The inhibitory effect induced by a maximally effective concentration of sarafotoxin S6c (10 nM; 72.1 +/- 5.7%, n = 6) was abolished in the presence of the ETB receptor-selective antagonist BQ-788 (1 microM) [4].
  • 1. The relative roles of ETA and ETB receptor activation on cholinergic nerve-mediated contraction and acetylcholine (ACh) release were examined in sheep isolated tracheal smooth muscle [4].

Chemical compound and disease context of ETBR


Biological context of ETBR


Anatomical context of ETBR

  • Endothelin-1, via activation of an ETB receptor, inhibits cholinergic nerve-mediated contractions in sheep trachea [10].
  • Chemical crosslinking of [125I]ET-1 with bis(sulfosuccinimidyl)-suberate (BS3) to choroid plexus membranes revealed the presence of two bands, with apparent molecular masses of 89 and 45 kDa, corresponding to the ETA receptor, and three bands, with apparent molecular masses of 75, 58, and 33 kDa, corresponding to the ETB receptor [11].
  • In contrast, protein expression levels of ETA and ETB receptor were significantly lower in the vascular smooth muscle cells among other tissue subcompartments of the right lung of treated CDH newborn lambs vs CDH lambs (P < .02 and P = .005, respectively) [12].

Associations of ETBR with chemical compounds

  • BQ 123 (1 microM) also abolished specific binding to structures associated with submucosal glands, whereas the ETB receptor selective agonist, sarafotoxin S6c (100 nM) had little effect on this binding, indicating the predominance of ETA receptors at these sites [13].
  • Twelve sheep received S+B injury using the following protocol: six sheep were treated with tezosentan, an ETA and ETB receptor antagonist, and six sheep received an equivalent volume of vehicle [14].
  • The hemodynamic responses to endothelium-dependent (acetylcholine, ATP, ET-1, and 4 Ala ET-1 [an ETb receptor agonist]) and endothelium-independent (nitroprusside and isoproterenol) vasodilators were compared [8].
  • METHODS: The effect of atrasentan on protein expression levels of ETs and ET receptors (ETA and ETB receptor) was investigated by immunohistochemistry in lung tissues of untreated control (n = 3), treated control (n = 6), untreated CDH (n = 6), and treated CDH newborn lambs (n = 8) [12].

Analytical, diagnostic and therapeutic context of ETBR


  1. Prolonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus. Ivy, D.D., Parker, T.A., Abman, S.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  2. Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure. Fratz, S., Meyrick, B., Ovadia, B., Johengen, M.J., Reinhartz, O., Azakie, A., Ross, G., Fitzgerald, R., Oishi, P., Hess, J., Black, S.M., Fineman, J.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  3. Coordinated regulation of genes of the nitric oxide and endothelin pathways during the development of pulmonary hypertension in fetal lambs. Black, S.M., Johengen, M.J., Soifer, S.J. Pediatr. Res. (1998) [Pubmed]
  4. Inhibition by endothelin-1 of cholinergic nerve-mediated acetylcholine release and contraction in sheep isolated trachea. Henry, P.J., Shen, A., Mitchelson, F., Goldie, R.G. Br. J. Pharmacol. (1996) [Pubmed]
  5. Increased lung preproET-1 and decreased ETB-receptor gene expression in fetal pulmonary hypertension. Ivy, D.D., Le Cras, T.D., Horan, M.P., Abman, S.H. Am. J. Physiol. (1998) [Pubmed]
  6. The role of endothelin and endothelin receptor subtypes in regulation of fetal pulmonary vascular tone. Wong, J., Fineman, J.R., Heymann, M.A. Pediatr. Res. (1994) [Pubmed]
  7. Endothelin receptor blockade does not alter the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs. Winters, J.W., Wong, J., Van Dyke, D., Johengen, M., Heymann, M.A., Fineman, J.R. Pediatr. Res. (1996) [Pubmed]
  8. Altered endothelial function in lambs with pulmonary hypertension and acute lung injury. Fineman, J.R., Wong, J., Mikhailov, T., Vanderford, P.A., Jerome, H.E., Soifer, S.J. Pediatr. Pulmonol. (1999) [Pubmed]
  9. Altered ETB- but not ETA-receptor density and function in sheep airway smooth muscle cells in culture. Maxwell, M.J., Goldie, R.G., Henry, P.J. Am. J. Physiol. (1998) [Pubmed]
  10. Endothelin-1, via activation of an ETB receptor, inhibits cholinergic nerve-mediated contractions in sheep trachea. Henry, P.J., Goldie, R.G. J. Cardiovasc. Pharmacol. (1995) [Pubmed]
  11. Identification of endothelin receptor subtypes in sheep choroid plexus. Angelova, K., Puett, D., Narayan, P. Endocrine (1997) [Pubmed]
  12. Modulating effect of a selective endothelin A receptor antagonist on pulmonary endothelin system protein expression in experimental diaphragmatic hernia. Kavanagh, M., Seaborn, T., Crochetière, J., Fournier, L., Battistini, B., Piedboeuf, B., Major, D. J. Pediatr. Surg. (2005) [Pubmed]
  13. Predominance of endothelinA (ETA) receptors in ovine airway smooth muscle and their mediation of ET-1-induced contraction. Goldie, R.G., Grayson, P.S., Knott, P.G., Self, G.J., Henry, P.J. Br. J. Pharmacol. (1994) [Pubmed]
  14. Effects of a dual endothelin-1 receptor antagonist on airway obstruction and acute lung injury in sheep following smoke inhalation and burn injury. Cox, R.A., Enkhabaatar, P., Burke, A.S., Katahira, J., Shimoda, K., Chandra, A., Traber, L.D., Herndon, D.N., Hawkins, H.K., Traber, D.L. Clin. Sci. (2005) [Pubmed]
  15. Endothelin B receptor blockade attenuates pulmonary vasodilation in oxygen-ventilated fetal lambs. Ivy, D.D., Lee, D.S., Rairigh, R.L., Parker, T.A., Abman, S.H. Biol. Neonate (2004) [Pubmed]
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