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Gene Review

Edn2  -  endothelin 2

Mus musculus

Synonyms: ET-2, Endothelin-2, PPET2, Preproendothelin-2, VIC, ...
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Disease relevance of Edn2


High impact information on Edn2

  • The significant residual ET-1/ET-2 in the ECE-1(-/-); ECE-2(-/-) embryos indicates that proteases distinct from ECE-1 and ECE-2 can carry out ET-1 activation in vivo [4].
  • Taken together these observations suggest that VIC may have contractile properties, which can account for a controlled tonus, actively correlated with the cyclically changing forces acting on valves during diastole and systole [5].
  • Furthermore, bombesin, vasopressin, and VIC markedly increased the rate of phosphorylation of Raytide, a broad specificity tyrosine kinase peptide substrate, by decreasing (8 +/- 1.3-fold) the apparent Km of the kinase for the substrate [6].
  • Neuropeptides increased the labeling of p115 within seconds and with great potency; half-maximum concentrations were 0.1, 0.2 and 0.3 nM for bombesin, vasopressin, and VIC, respectively [6].
  • We also identified cGMP-dependent protein kinase II, a previously reported PGR-regulated gene, as a downstream target of ET-2 during ovulation [7].

Biological context of Edn2


Anatomical context of Edn2


Associations of Edn2 with chemical compounds

  • The endothelin-related peptide, vasoactive intestinal contractor, also elicited a rapid and concentration-dependent tyrosine/serine phosphorylation of a similar set of substrates [12].
  • Lowering the extracellular concentration of calcium by the addition of 1 mmol/liter EGTA did not inhibit the effect of ET-2 on cAMP induced renin secretion and renin gene expression [13].
  • The inhibitory effects of [D-Arg1,D-Phe5,D-Trp7,9,Leu 11] substance P on Ca2+ mobilization and DNA synthesis were reversed by increasing the concentration of VIC [14].
  • In this study, biphasic Ca(2+) signals elicited with endothelin (ET)-1, ET-2, ET-3, beta-ET, S6a1, and S6b (ET/S6) were measured by microspectrofluorimetric methods in cell suspensions loaded with Fura-2 acetoxymethylester (Fura-2 AM) [15].

Physical interactions of Edn2

  • This is the first time that a peptide structurally unrelated to ET1 or VIC is shown to block the binding and mitogenic effects of peptides of the endothelin family [14].

Regulatory relationships of Edn2


Other interactions of Edn2


Analytical, diagnostic and therapeutic context of Edn2


  1. Primary structure of cat preproendothelin-2 and cat renal mRNA expression of preproendothelin-1 and preproendothelin-2 in naturally occurring renal failure. Uchide, T., Saida, K. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  2. The prepro vasoactive intestinal contractor (VIC)/endothelin-2 gene (EDN2): structure, evolution, production, and embryonic expression. Saida, K., Hashimoto, M., Mitsui, Y., Ishida, N., Uchide, T. Genomics (2000) [Pubmed]
  3. The endothelin-2/vasoactive intestinal contractor gene: expression and promoter activity in PC12 rat pheochromocytoma cells. Saida, K., Uchide, T., Usui, A., Gao, X.D., Tomizuka, N., Oka, S., Masuda, H. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
  4. Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development. Yanagisawa, H., Hammer, R.E., Richardson, J.A., Emoto, N., Williams, S.C., Takeda, S., Clouthier, D.E., Yanagisawa, M. J. Clin. Invest. (2000) [Pubmed]
  5. Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells. Filip, D.A., Radu, A., Simionescu, M. Circ. Res. (1986) [Pubmed]
  6. Stimulation of tyrosine kinase activity in anti-phosphotyrosine immune complexes of Swiss 3T3 cell lysates occurs rapidly after addition of bombesin, vasopressin, and endothelin to intact cells. Zachary, I., Sinnett-Smith, J., Rozengurt, E. J. Biol. Chem. (1991) [Pubmed]
  7. A novel pathway involving progesterone receptor, endothelin-2, and endothelin receptor B controls ovulation in mice. Palanisamy, G.S., Cheon, Y.P., Kim, J., Kannan, A., Li, Q., Sato, M., Mantena, S.R., Sitruk-Ware, R.L., Bagchi, M.K., Bagchi, I.C. Mol. Endocrinol. (2006) [Pubmed]
  8. Gene expression of vasoactive intestinal contractor/endothelin-2 in ovary, uterus and embryo: comprehensive gene expression profiles of the endothelin ligand-receptor system revealed by semi-quantitative reverse transcription-polymerase chain reaction analysis in adult mouse tissues and during late embryonic development. Uchide, T., Masuda, H., Mitsui, Y., Saida, K. J. Mol. Endocrinol. (1999) [Pubmed]
  9. Sequence analysis and expression of the mouse full-length vasoactive intestinal contractor/endothelin-2 gene (EDN2): comparison with the endothelin-1 gene (EDN1). Saida, K., Kometani, N., Uchide, T., Mitsui, Y. Clin. Sci. (2002) [Pubmed]
  10. Vasoactive intestinal contractor/endothelin-2 gene expression in the murine central nervous system. Masuo, Y., Ishikawa, Y., Kozakai, T., Uchide, T., Komatsu, Y., Saida, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  11. Increased gene expression of endothelin-1 and vasoactive intestinal contractor/endothelin-2 in the mammary gland of lactating mice. Kozakai, T., Sakate, M., Masuo, Y., Uchide, T., Saida, K. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  12. Bombesin, vasopressin, and endothelin rapidly stimulate tyrosine phosphorylation in intact Swiss 3T3 cells. Zachary, I., Gil, J., Lehmann, W., Sinnett-Smith, J., Rozengurt, E. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  13. Endothelins inhibit cyclic-AMP induced renin gene expression in cultured mouse juxtaglomerular cells. Ritthaler, T., Della Bruna, R., Krämer, B.K., Kurtz, A. Kidney Int. (1996) [Pubmed]
  14. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P, a neuropeptide antagonist, blocks binding, Ca2(+)-mobilizing, and mitogenic effects of endothelin and vasoactive intestinal contractor in mouse 3T3 cells. Fabregat, I., Rozengurt, E. J. Cell. Physiol. (1990) [Pubmed]
  15. Endothelin- and sarafotoxin-induced receptor-mediated calcium mobilization in a clonal murine osteoblast-like cell line, MC3T3-E1/B. Zach, D., Windischhofer, W., Leis, H.J. Bone (2001) [Pubmed]
  16. Inhibition of endothelin (ET)-1-and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody. Koshi, T., Torii, T., Arai, K., Edano, T., Hirata, M., Ohkuchi, M., Okabe, T. Chem. Pharm. Bull. (1991) [Pubmed]
  17. Endothelin-1, -2 and -3 directly and big-endothelin-1 indirectly elicit an abdominal constriction response in mice. Raffa, R.B., Jacoby, H.I. Life Sci. (1991) [Pubmed]
  18. A novel peptide, vasoactive intestinal contractor, of a new (endothelin) peptide family. Molecular cloning, expression, and biological activity. Saida, K., Mitsui, Y., Ishida, N. J. Biol. Chem. (1989) [Pubmed]
  19. Rapid quantification of murine endothelin-1 and vasoactive intestinal contractor gene expression levels by a real-time PCR system. Uchide, T., Adur, J., Saida, K. J. Biotechnol. (2001) [Pubmed]
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