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Gene Review

EDNRB  -  endothelin receptor type B

Bos taurus

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Disease relevance of EDNRB

  • These data suggest that endothelins stimulate ETB receptor-mediated phosphoinositide breakdown via pertussis toxin-sensitive G-protein(s), which triggers release of intracellular Ca2+, thereby activating Ca2+/calmodulin-dependent NO synthase in EC [1].

High impact information on EDNRB

  • Binding studies revealed that bovine EC membrane had the binding sites of a novel agonist (BQ3020) for non-isopeptide-selective receptor subtype (ETB) [1].
  • The stimulatory effect on NOx and cGMP production by ETB agonist was inhibited by NO synthase inhibitor monomethyl-L-arginine; this effect was reversed by coaddition of L-arginine, but not D-arginine [1].
  • A comparison of the predicted amino acid sequence with the available bovine ETA and rat ETB endothelin receptor sequences revealed 63 and 85% homology, respectively [2].
  • A cDNA clone corresponding to the entire coding region of the bovine ETB endothelin receptor mRNA was isolated from a lung cDNA library and sequenced [2].
  • To probe in the isolated bovine corneal epithelium (BCE) for ET isoform and ET (i.e., ETA and ETB) receptor gene expression [3].

Biological context of EDNRB

  • The amino acid sequence (Ala-Gly-X-Pro-Pro-Arg) surrounding the cleavage site (between Ala-79 and Gly-80) is conserved among the ETB endothelin receptors, explaining the above mentioned proteolytic conversion from the higher to lower Mr forms observed in various species [2].
  • ETA gene expression was appreciably higher in the basal cells than in the suprabasal cells, whereas the pattern for ETB was reversed [4].
  • Physical mapping of the endothelin receptor type B to bovine chromosome 12 [5].
  • RES-1149-1 and -2 selectively inhibited the ET-1 binding to endothelin type B receptor (ETB receptor) with IC50 values of 1.5 microM and 20 microM, respectively [6].
  • The endothelin receptor type B (ETR-B) mRNA expression increased during late luteal phase and further after regression [7].

Anatomical context of EDNRB


Associations of EDNRB with chemical compounds

  • The increased transcription can be attributed to ETB receptor blockade, because BQ-788, but not BQ-123, increased PPE-1 transcription [11].
  • Bosentan, a dual ETA/B receptor antagonist, and BQ788 (ETB receptor antagonist) treatment resulted in a 1.6-fold and 1.3-fold increase, respectively in luciferase activity as compared with the untreated control [11].
  • After treatment with 10(-7) M alltrans retinoic acid (an inducer of differentiation), 10(-6) M sarafotoxin (S-6-c) (a selective ETB agonist), had a similar effect [3].
  • ET-1 inhibition of histamine-induced [(3)H]cyclic AMP was reversed by the ET-A receptor antagonist BQ-123 while the ET-B receptor antagonist BQ-788 had no effect [12].
  • These data suggest that endothelial ETB receptors are functionally coupled to adenylate cyclase, possibly via Gi protein [13].

Analytical, diagnostic and therapeutic context of EDNRB

  • Northern blot analysis demonstrated the expression of mRNA for ETB receptor [1].
  • The C-terminal hexapeptide ET-1[16-21], which has been reported as an ETB receptor agonist but which gave no reactivity in the ELISA, also was investigated [14].
  • Affinity cross-linking of the receptors showed two distinct protein bands on SDS-PAGE of 66 and 45 kd, corresponding to ETA and ETB [8].
  • In situ hybridization histochemistry was used to characterize ETA and ETB gene expression in the BCE [4].


  1. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. Hirata, Y., Emori, T., Eguchi, S., Kanno, K., Imai, T., Ohta, K., Marumo, F. J. Clin. Invest. (1993) [Pubmed]
  2. Primary structure of bovine endothelin ETB receptor and identification of signal peptidase and metal proteinase cleavage sites. Saito, Y., Mizuno, T., Itakura, M., Suzuki, Y., Ito, T., Hagiwara, H., Hirose, S. J. Biol. Chem. (1991) [Pubmed]
  3. Endothelin receptor-mediated Ca2+ signaling and isoform expression in bovine corneal epithelial cells. Tao, W., Wu, X., Liou, G.I., Abney, T.O., Reinach, P.S. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  4. ETB and epidermal growth factor receptor stimulation of wound closure in bovine corneal epithelial cells. Tao, W., Liou, G.I., Wu, X., Abney, T.O., Reinach, P.S. Invest. Ophthalmol. Vis. Sci. (1995) [Pubmed]
  5. Physical mapping of the endothelin receptor type B to bovine chromosome 12. Schläpfer, J., Gallagher, D.S., Burzlaff, J.D., Davis, S.K., Taylor, J.F., Womack, J.E. Mamm. Genome (1997) [Pubmed]
  6. RES-1149-1 and -2, novel non-peptidic endothelin type B receptor antagonists produced by Aspergillus sp. I. Taxonomy of producing strain, fermentation, isolation, and physico-chemical and biological properties. Ogawa, T., Ando, K., Tanaka, T., Uosaki, Y., Matsuda, Y. J. Antibiot. (1996) [Pubmed]
  7. The expression of angiotensin and endothelin system members in bovine corpus luteum during estrous cycle and pregnancy. Berisha, B., Schams, D., Miyamoto, A. Endocrine (2002) [Pubmed]
  8. Characterization of endothelin A (ETA) and endothelin B (ETB) receptors in cultured bovine retinal pericytes. McDonald, D.M., Bailie, J.R., Archer, D.B., Chakravarthy, U. Invest. Ophthalmol. Vis. Sci. (1995) [Pubmed]
  9. Delphinidin-3-rutinoside relaxes the bovine ciliary smooth muscle through activation of ETB receptor and NO/cGMP pathway. Matsumoto, H., Kamm, K.E., Stull, J.T., Azuma, H. Exp. Eye Res. (2005) [Pubmed]
  10. Endothelium localization of ETB receptor revealed by immunohistochemistry. Ghoneim, M.A., Yamamoto, T., Hirose, S., Nagasawa, T., Hagiwara, H. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
  11. Endothelin B receptor antagonist increases preproendothelin-1 transcription in bovine aortic endothelial cells and in vivo. Peled, M., Shaish, A., Frishman, L., Cohen, H., Tal, R., Harats, D. J. Cardiovasc. Pharmacol. (2006) [Pubmed]
  12. Endothelin inhibits histamine-induced cyclic AMP accumulation in bovine brain vessels. Hernández, F., Martínez, A.M., Piedra, D., Catalán, R.E. Microvasc. Res. (2000) [Pubmed]
  13. Endothelin subtype B receptors are coupled to adenylate cyclase via inhibitory G protein in cultured bovine endothelial cells. Eguchi, S., Hirata, Y., Marumo, F. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
  14. Receptor binding and biologic activity of synthetic ET-1 peptides in the retinal pericyte. McDonald, D.M., Bailie, J.R., Archer, D.B., Chakravarthy, U. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
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