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Gene Review

EDN1  -  endothelin 1

Sus scrofa

Synonyms: EDN, ET-1, ET1, PPET1
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Disease relevance of EDN1


Psychiatry related information on EDN1

  • In the combination therapy group, the relative increase in catecholamines and endothelin with exercise were significantly blunted when compared to rapid pacing only values [6].

High impact information on EDN1

  • An endothelium-derived 21-residue vasoconstrictor peptide, endothelin, has been isolated, and shown to be one of the most potent vasoconstrictors known [7].
  • Endothelin was detected in the incubating medium of unstimulated pig aortae with, but not in those without endothelium [8].
  • Thus, (a) endothelin is released from the intimal layer of intact blood vessels, both under basal conditions and after stimulation with thrombin and the calcium ionophore A23187, and (b) endothelium-derived nitric oxide released during stimulation with thrombin inhibits the production of the peptide via a cyclic GMP-dependent pathway [8].
  • The basal and thrombin-stimulated production of endothelin were prevented by the protein synthetase inhibitor cycloheximide (10(-6) M) [8].
  • The production of endothelin upon stimulation with thrombin (4 U/ml) was potentiated by L-NG-monomethyl arginine and methylene blue and reduced by superoxide dismutase and 8-bromo cyclic guanosine 5'-monophosphate (GMP), while the basal release of the peptide was unaffected [8].

Chemical compound and disease context of EDN1


Biological context of EDN1


Anatomical context of EDN1


Associations of EDN1 with chemical compounds

  • Additional experiments indicated that the properistaltic action of endothelin 1 is mediated by enteric neurons, whereas the peristaltic motor effects of sarafotoxin 6c and BQ-788 are caused by a direct action on the muscle [16].
  • The ET(A) receptor antagonist BQ-123 (3 micromol/L) converted the properistaltic action of endothelin 1 to an antiperistaltic action, whereas the ET(B) receptor antagonist BQ-788 (3 micromol/L) prevented the antiperistaltic action of sarafotoxin 6c [16].
  • Chronic endothelin receptor antagonism significantly increased coronary blood flow in response to acetylcholine at 12 weeks (group 1: -41.6%+/-10.7%, group 2: -4.7%+/-11.9%, group 3: 11.4%+/-7.4%) [21].
  • Plasma norepinephrine and endothelin increased by more than fivefold with chronic pacing and remained elevated with AT1 Ang II blockade [22].
  • Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle [18].

Enzymatic interactions of EDN1


Regulatory relationships of EDN1


Other interactions of EDN1


Analytical, diagnostic and therapeutic context of EDN1


  1. Contribution of endothelin to coronary vasomotor tone is abolished after myocardial infarction. Merkus, D., Houweling, B., van den Meiracker, A.H., Boomsma, F., Duncker, D.J. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  2. Expression of endothelin-1 system in a pig model of endotoxic shock. Forni, M., Mazzola, S., Ribeiro, L.A., Pirrone, F., Zannoni, A., Bernardini, C., Bacci, M.L., Albertini, M. Regul. Pept. (2005) [Pubmed]
  3. Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs. Lerman, A., Webster, M.W., Chesebro, J.H., Edwards, W.D., Wei, C.M., Fuster, V., Burnett, J.C. Circulation (1993) [Pubmed]
  4. The effects of endothelin-A receptor blockade during the progression of pacing-induced congestive heart failure. Saad, D., Mukherjee, R., Thomas, P.B., Iannini, J.P., Basler, C.G., Hebbar, L., O, S.J., Moreland, S., Webb, M.L., Powell, J.R., Spinale, F.G. J. Am. Coll. Cardiol. (1998) [Pubmed]
  5. The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock. Oldner, A., Wanecek, M., Goiny, M., Weitzberg, E., Rudehill, A., Alving, K., Sollevi, A. Gut (1998) [Pubmed]
  6. Angiotensin converting enzyme inhibition, AT1 receptor inhibition, and combination therapy with pacing induced heart failure: effects on left ventricular performance and regional blood flow patterns. Krombach, R.S., Clair, M.J., Hendrick, J.W., Houck, W.V., Zellner, J.L., Kribbs, S.B., Whitebread, S., Mukherjee, R., de Gasparo, M., Spinale, F.G. Cardiovasc. Res. (1998) [Pubmed]
  7. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., Masaki, T. Nature (1988) [Pubmed]
  8. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. Boulanger, C., Lüscher, T.F. J. Clin. Invest. (1990) [Pubmed]
  9. Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. Lerman, A., Holmes, D.R., Bell, M.R., Garratt, K.N., Nishimura, R.A., Burnett, J.C. Circulation (1995) [Pubmed]
  10. Effects of endothelin on hemodynamics, prostaglandins, blood coagulation and renal function. Schulz, E., Ruschitzka, F., Lueders, S., Heydenbluth, R., Schrader, J., Müller, G.A. Kidney Int. (1995) [Pubmed]
  11. Pharmacologic graft protection without donor pretreatment in liver transplantation from non-heart-beating donors. Gu, M., Takada, Y., Fukunaga, K., Ishiguro, S., Taniguchi, H., Seino, K., Yuzawa, K., Otsuka, M., Todoroki, T., Fukao, K. Transplantation (2000) [Pubmed]
  12. Endothelin receptor antagonist bosentan improves microcirculatory blood flow in splanchnic organs in septic shock. Krejci, V., Hiltebrand, L.B., Erni, D., Sigurdsson, G.H. Crit. Care Med. (2003) [Pubmed]
  13. Effects of endothelin receptor antagonism on acute lung injury induced by chlorine gas. Wang, J., Oldner, A., Winskog, C., Edston, E., Walther, S.M. Crit. Care Med. (2006) [Pubmed]
  14. An EcoRI RFLP at the porcine endothelin-1 locus (EDN1). Couperwhite, S., Archibald, A.L. Anim. Genet. (1994) [Pubmed]
  15. Structural organization and chromosomal assignment of the swine endothelin-1 gene. Kojima, M., Ohata, K., Yasue, H. J. Vet. Med. Sci. (1997) [Pubmed]
  16. Regulation of guinea pig intestinal peristalsis by endogenous endothelin acting at ET(B) receptors. Shahbazian, A., Holzer, P. Gastroenterology (2000) [Pubmed]
  17. Two endothelin receptors (ETA and ETB) expressed on circular smooth muscle cells of guinea pig cecum. Okabe, H., Chijiiwa, Y., Nakamura, K., Yoshinaga, M., Akiho, H., Harada, N., Nawata, H. Gastroenterology (1995) [Pubmed]
  18. Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle. Goto, K., Kasuya, Y., Matsuki, N., Takuwa, Y., Kurihara, H., Ishikawa, T., Kimura, S., Yanagisawa, M., Masaki, T. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  19. Selective ET(A) receptor antagonism reduces neointimal hyperplasia in a porcine coronary stent model. McKenna, C.J., Burke, S.E., Opgenorth, T.J., Padley, R.J., Camrud, L.J., Camrud, A.R., Johnson, J., Carlson, P.J., Lerman, A., Holmes, D.R., Schwartz, R.S. Circulation (1998) [Pubmed]
  20. Hirudin and nitrates inhibit the thrombin-induced release of endothelin from the intact porcine aorta. Boulanger, C.M., Lüscher, T.F. Circ. Res. (1991) [Pubmed]
  21. Chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia. Best, P.J., McKenna, C.J., Hasdai, D., Holmes, D.R., Lerman, A. Circulation (1999) [Pubmed]
  22. Modulation of the renin-angiotensin pathway through enzyme inhibition and specific receptor blockade in pacing-induced heart failure: I. Effects on left ventricular performance and neurohormonal systems. Spinale, F.G., de Gasparo, M., Whitebread, S., Hebbar, L., Clair, M.J., Melton, D.M., Krombach, R.S., Mukherjee, R., Iannini, J.P., O, S.J. Circulation (1997) [Pubmed]
  23. Metallopeptidase inhibitors induce an up-regulation of endothelin-converting enzyme levels and its redistribution from the plasma membrane to an intracellular compartment. Barnes, K., Shimada, K., Takahashi, M., Tanzawa, K., Turner, A.J. J. Cell. Sci. (1996) [Pubmed]
  24. Transforming growth factor-beta stimulates the expression of endothelin mRNA by vascular endothelial cells. Kurihara, H., Yoshizumi, M., Sugiyama, T., Takaku, F., Yanagisawa, M., Masaki, T., Hamaoki, M., Kato, H., Yazaki, Y. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  25. Tetrahydrobiopterin attenuates cholesterol induced coronary hyperreactivity to endothelin. Verma, S., Dumont, A.S., Maitland, A. Heart (2001) [Pubmed]
  26. Expression and function of endothelins, endothelin receptors, and endothelin converting enzyme in the porcine trachea. Yoshimura, H., Nishimura, J., Sakihara, C., Kobayashi, S., Takahashi, S., Kanaide, H. Am. J. Respir. Cell Mol. Biol. (1997) [Pubmed]
  27. Effect of acute brain death on release of atrium and B-type natriuretic peptides in an animal model. Potapov, E.V., Blömer, T., Michael, R., Hennig, F., Müller, C., Loebe, M., Skrabal, C., Hetzer, R. Transplantation (2004) [Pubmed]
  28. Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c. Hasdai, D., Holmes, D.R., Richardson, D.M., Izhar, U., Lerman, A. Cardiovasc. Res. (1998) [Pubmed]
  29. Endothelin-like pulmonary vasoconstrictor peptide release by alpha-thrombin. Moon, D.G., Horgan, M.J., Andersen, T.T., Krystek, S.R., Fenton, J.W., Malik, A.B. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  30. Cocaine increases the endothelial release of immunoreactive endothelin and its concentrations in human plasma and urine: reversal by coincubation with sigma-receptor antagonists. Wilbert-Lampen, U., Seliger, C., Zilker, T., Arendt, R.M. Circulation (1998) [Pubmed]
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