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Gene Review

Edn1  -  endothelin 1

Rattus norvegicus

Synonyms: ET-1, Endothelin-1, PPET1, Preproendothelin-1
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Disease relevance of Edn1


Psychiatry related information on Edn1


High impact information on Edn1


Chemical compound and disease context of Edn1


Biological context of Edn1


Anatomical context of Edn1


Associations of Edn1 with chemical compounds

  • The effects of ET-1 on ECE-1 mRNA and protein expression were shown to be mimicked by ionomycin, a calcium ionophore, but not by 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator [22].
  • Endothelin (ET), a potent vasoconstrictor peptide, is known to enhance the secretion of atrial natriuretic factor (ANF) by the heart [24].
  • The specificity of the cardiovascular response to endothelin was demonstrated by the inhibitory effects of the receptor antagonist BQ-123 [3].
  • In sinoaortic-denervated animals, phenylephrine failed to reduce CSF endothelin levels [3].
  • The relevance of endothelin in central cardiovascular function was studied in urethane-anesthetized Sprague-Dawley rats [3].

Physical interactions of Edn1

  • Although it is commonly accepted that endothelin-1 binding to endothelial cell ETB receptors stimulates nitric oxide (NO) synthesis and subsequent smooth muscle relaxation, the signaling pathways downstream of ETB receptor activation are unknown [25].
  • The ET-1- binding sites were predominantly of ETA subtype since BQ123, but not IRL1038 (ETB receptor subtype agonist), effectively blocked 125I-ET-1 binding [26].
  • Protein kinase C and protein tyrosine kinase activity contribute to mitogenic signaling by endothelin-1. Cross-talk between G protein-coupled receptors and pp60c-src [27].
  • 125I-ET-1 binding was inhibited by ET-1 with an IC50 value of 0.17 nM but was only partially (approximately 60%) inhibited by 1 microM ET-3 [28].
  • Endothelin receptor subtypes are coupled to adenylate cyclase via different guanyl nucleotide-binding proteins in vasculature [29].

Enzymatic interactions of Edn1


Co-localisations of Edn1


Regulatory relationships of Edn1


Other interactions of Edn1

  • LPS significantly inhibited ET-1-mediated eNOS activation [5].
  • Antagonizing ET-1 effects and blocking its activation in LPS pretreated SECs decreased the LPS-induced overexpression of CAV-1 as well as the inhibition of ET-1-induced NOS activity [5].
  • Endothelin-1-specific activation of B-type natriuretic peptide gene via p38 mitogen-activated protein kinase and nuclear ETS factors [35].
  • Dexamethasone decreased ET-1-stimulated PGE2 release and COX-2 protein and mRNA levels [37].
  • ET-1 rapidly increased association of EGFR and Shc with glutathione-S-transferase-Grb2 fusion protein [38].

Analytical, diagnostic and therapeutic context of Edn1


  1. Role of the stress-activated protein kinases in endothelin-induced cardiomyocyte hypertrophy. Choukroun, G., Hajjar, R., Kyriakis, J.M., Bonventre, J.V., Rosenzweig, A., Force, T. J. Clin. Invest. (1998) [Pubmed]
  2. Endothelin-3 induces hypertrophy of cardiomyocytes by the endogenous endothelin-1-mediated mechanism. Tamamori, M., Ito, H., Adachi, S., Akimoto, H., Marumo, F., Hiroe, M. J. Clin. Invest. (1996) [Pubmed]
  3. Endothelin as a neuropeptide. Cardiovascular effects in the brainstem of normotensive rats. Mosqueda-Garcia, R., Inagami, T., Appalsamy, M., Sugiura, M., Robertson, R.M. Circ. Res. (1993) [Pubmed]
  4. The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat. Ling, Y., Zhang, J., Luo, B., Song, D., Liu, L., Tang, L., Stockard, C.R., Grizzle, W.E., Ku, D.D., Fallon, M.B. Hepatology (2004) [Pubmed]
  5. LPS inhibits endothelin-1-induced endothelial NOS activation in hepatic sinusoidal cells through a negative feedback involving caveolin-1. Kamoun, W.S., Karaa, A., Kresge, N., Merkel, S.M., Korneszczuk, K., Clemens, M.G. Hepatology (2006) [Pubmed]
  6. Effect of endothelin-1, endothelin-3 and C-terminal hexapeptide, endothelin (16-21) on motor activity in rats. Lecci, A., Maggi, C.A., Rovero, P., Giachetti, A., Meli, A. Neuropeptides (1990) [Pubmed]
  7. Chronic ethanol sensitizes the liver to endotoxin via effects on endothelial nitric oxide synthase regulation. Karaa, A., Kamoun, W.S., Clemens, M.G. Shock (2005) [Pubmed]
  8. Alterations in buccal mucosal endothelin-1 and nitric oxide synthase with chronic alcohol ingestion. Slomiany, B.L., Piotrowski, J., Slomiany, A. Biochem. Mol. Biol. Int. (1998) [Pubmed]
  9. Endothelin: a novel peptide in the posterior pituitary system. Yoshizawa, T., Shinmi, O., Giaid, A., Yanagisawa, M., Gibson, S.J., Kimura, S., Uchiyama, Y., Polak, J.M., Masaki, T., Kanazawa, I. Science (1990) [Pubmed]
  10. Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats. Stocker, S.D., Stricker, E.M., Sved, A.F. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  11. Uridine adenosine tetraphosphate: a novel endothelium- derived vasoconstrictive factor. Jankowski, V., Tölle, M., Vanholder, R., Schönfelder, G., van der Giet, M., Henning, L., Schlüter, H., Paul, M., Zidek, W., Jankowski, J. Nat. Med. (2005) [Pubmed]
  12. Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Khodorova, A., Navarro, B., Jouaville, L.S., Murphy, J.E., Rice, F.L., Mazurkiewicz, J.E., Long-Woodward, D., Stoffel, M., Strichartz, G.R., Yukhananov, R., Davar, G. Nat. Med. (2003) [Pubmed]
  13. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Chitaley, K., Wingard, C.J., Clinton Webb, R., Branam, H., Stopper, V.S., Lewis, R.W., Mills, T.M. Nat. Med. (2001) [Pubmed]
  14. Myosin light chain kinase mediates sarcomere organization during cardiac hypertrophy in vitro. Aoki, H., Sadoshima, J., Izumo, S. Nat. Med. (2000) [Pubmed]
  15. Extracellular signal-regulated kinase plays an essential role in hypertrophic agonists, endothelin-1 and phenylephrine-induced cardiomyocyte hypertrophy. Yue, T.L., Gu, J.L., Wang, C., Reith, A.D., Lee, J.C., Mirabile, R.C., Kreutz, R., Wang, Y., Maleeff, B., Parsons, A.A., Ohlstein, E.H. J. Biol. Chem. (2000) [Pubmed]
  16. Endothelin stimulates mitogen-activated protein kinase activity in mesangial cells through ETA. Wang, Y., Pouysségur, J., Dunn, M.J. J. Am. Soc. Nephrol. (1994) [Pubmed]
  17. Mechanisms of FK 506-induced hypertension in the rat. Takeda, Y., Miyamori, I., Furukawa, K., Inaba, S., Mabuchi, H. Hypertension (1999) [Pubmed]
  18. Endothelin converting enzyme-1 gene expression in the kidney of spontaneously hypertensive rats. Disashi, T., Nonoguchi, H., Iwaoka, T., Naomi, S., Nakayama, Y., Shimada, K., Tanzawa, K., Tomita, K. Hypertension (1997) [Pubmed]
  19. Cyclic expression of endothelin-converting enzyme-1 mediates the functional regulation of seminiferous tubule contraction. Tripiciano, A., Peluso, C., Morena, A.R., Palombi, F., Stefanini, M., Ziparo, E., Yanagisawa, M., Filippini, A. J. Cell Biol. (1999) [Pubmed]
  20. Characteristics of binding of endothelin-1 and endothelin-3 to rat hearts. Developmental changes in mechanical responses and receptor subtypes. Ishikawa, T., Li, L.M., Shinmi, O., Kimura, S., Yanagisawa, M., Goto, K., Masaki, T. Circ. Res. (1991) [Pubmed]
  21. Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells. Owada, A., Tomita, K., Terada, Y., Sakamoto, H., Nonoguchi, H., Marumo, F. J. Clin. Invest. (1994) [Pubmed]
  22. Endothelin-1 inhibits endothelin-converting enzyme-1 expression in cultured rat pulmonary endothelial cells. Naomi, S., Iwaoka, T., Disashi, T., Inoue, J., Kanesaka, Y., Tokunaga, H., Tomita, K. Circulation (1998) [Pubmed]
  23. Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1. Housset, C., Rockey, D.C., Bissell, D.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  24. Endothelin-stimulated secretion of natriuretic peptides by rat atrial myocytes is mediated by endothelin A receptors. Thibault, G., Doubell, A.F., Garcia, R., Larivière, R., Schiffrin, E.L. Circ. Res. (1994) [Pubmed]
  25. Endothelin-1 activates endothelial cell nitric-oxide synthase via heterotrimeric G-protein betagamma subunit signaling to protein jinase B/Akt. Liu, S., Premont, R.T., Kontos, C.D., Huang, J., Rockey, D.C. J. Biol. Chem. (2003) [Pubmed]
  26. Endothelin-1 receptors on cultured rat articular chondrocytes: regulation by age, growth factors, and cytokines, and effect on cAMP production. Messai, H., Panasyuk, A., Khatib, A., Barbara, A., Mitrovic, D.R. Mech. Ageing Dev. (2001) [Pubmed]
  27. Protein kinase C and protein tyrosine kinase activity contribute to mitogenic signaling by endothelin-1. Cross-talk between G protein-coupled receptors and pp60c-src. Simonson, M.S., Herman, W.H. J. Biol. Chem. (1993) [Pubmed]
  28. Identification and characterization of type A endothelin receptors in MMQ cells. Wu-Wong, J.R., Chiou, W., Magnuson, S.R., Witte, D.G., Lin, C.W. Mol. Pharmacol. (1993) [Pubmed]
  29. Endothelin receptor subtypes are coupled to adenylate cyclase via different guanyl nucleotide-binding proteins in vasculature. Eguchi, S., Hirata, Y., Imai, T., Marumo, F. Endocrinology (1993) [Pubmed]
  30. Differential activation of protein kinase C isoforms by endothelin-1 and phenylephrine and subsequent stimulation of p42 and p44 mitogen-activated protein kinases in ventricular myocytes cultured from neonatal rat hearts. Clerk, A., Bogoyevitch, M.A., Anderson, M.B., Sugden, P.H. J. Biol. Chem. (1994) [Pubmed]
  31. Involvement of p44/42 mitogen-activated protein kinases in regulating angiotensin II- and endothelin-1-induced contraction of rat thoracic aorta. Ishihata, A., Tasaki, K., Katano, Y. Eur. J. Pharmacol. (2002) [Pubmed]
  32. Expression of endothelin-converting enzyme in both neuroblastoma and glial cell lines and its localization in rat hippocampus. Barnes, K., Walkden, B.J., Wilkinson, T.C., Turner, A.J. J. Neurochem. (1997) [Pubmed]
  33. Cholangiocyte endothelin 1 and transforming growth factor beta1 production in rat experimental hepatopulmonary syndrome. Luo, B., Tang, L., Wang, Z., Zhang, J., Ling, Y., Feng, W., Sun, J.Z., Stockard, C.R., Frost, A.R., Chen, Y.F., Grizzle, W.E., Fallon, M.B. Gastroenterology (2005) [Pubmed]
  34. Big endothelin-1 but not endothelin-1 is present in the smooth muscle stroma of the prostate gland of the rat. Ventura, S., Salamoussa, A. J. Anat. (2002) [Pubmed]
  35. Endothelin-1-specific activation of B-type natriuretic peptide gene via p38 mitogen-activated protein kinase and nuclear ETS factors. Pikkarainen, S., Tokola, H., Kerkelä, R., Majalahti-Palviainen, T., Vuolteenaho, O., Ruskoaho, H. J. Biol. Chem. (2003) [Pubmed]
  36. Alterations in subcellular localization of p38 MAPK potentiates endothelin-stimulated COX-2 expression in glomerular mesangial cells. Pratt, P.F., Bokemeyer, D., Foschi, M., Sorokin, A., Dunn, M.J. J. Biol. Chem. (2003) [Pubmed]
  37. Endothelin-1 induction of cyclooxygenase-2 expression in rat mesangial cells. Hughes, A.K., Padilla, E., Kutchera, W.A., Michael, J.R., Kohan, D.E. Kidney Int. (1995) [Pubmed]
  38. Endothelin-mediated vascular growth requires p42/p44 mitogen-activated protein kinase and p70 S6 kinase cascades via transactivation of epidermal growth factor receptor. Iwasaki, H., Eguchi, S., Ueno, H., Marumo, F., Hirata, Y. Endocrinology (1999) [Pubmed]
  39. Endothelin 1 aggravates acute liver injury in perfused livers of rats after treatment with D-galactosamine. Iwai, M., Yamauchi, T., Shimazu, T. Hepatology (1998) [Pubmed]
  40. Crucial role of extracellular signal-regulated kinase pathway in reactive oxygen species-mediated endothelin-1 gene expression induced by endothelin-1 in rat cardiac fibroblasts. Cheng, C.M., Hong, H.J., Liu, J.C., Shih, N.L., Juan, S.H., Loh, S.H., Chan, P., Chen, J.J., Cheng, T.H. Mol. Pharmacol. (2003) [Pubmed]
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