The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Edn3  -  endothelin 3

Mus musculus

Synonyms: 114-CH19, 114CH19, ET-3, Endothelin-3, PPET3, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Edn3


Psychiatry related information on Edn3

  • ET-1 and ET-3 produced central depressive effects demonstrated by depressive behavior signs, decrease of the spontaneous and amphetamine-stimulated motor activity, and prolongation of the hexobarbital-induced narcosis [5].

High impact information on Edn3

  • The lethal-spotted mouse which has pigment abnormalities, but also colonic aganglionosis, carries a mutation in the gene coding for endothelin 3 (Edn3), the ligand for the receptor protein encoded by EDNRB [6].
  • A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome) [6].
  • Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons [7].
  • The targeted gene inactivation of endothelins-1 and -3 (ET-1 and ET-3) and of one of their receptors, ETB, in the mouse causes severe defects in the embryonic development [8].
  • Genetic data in the mouse have shown that endothelin 3 (ET3) and its receptor B (ETRB) are essential for the development of two neural crest (NC) derivatives, the melanocytes and the enteric nervous system [9].

Biological context of Edn3

  • Consistent with this, neither Ednrb nor Edn3 mRNA was detected in 3/3 tested immortal lines of mouse melanoblasts and 5/5 lines of melanocytes, of various genotypes [10].
  • Intravenous ET-1, ET-2, and ET-3 increased lung resistance similarly and equipotently, whereas S6c elicited a greater degree of bronchoconstriction [11].
  • The data from competitive binding experiments with [125I]ET-1 and unlabeled ET-1, ET-3 and receptor subtype selective ligands yielded a single class of high affinity binding sites with ETA receptor subtype characteristics [12].
  • RESULTS: ET-1, ET-3 and S6c (1-100 microM, 30 microliters) induced dose-dependent vasoconstriction of the portal venules, the sinusoids and the central venules [13].
  • Immunoblot analysis with an anti-phosphotyrosine antibody showed that ET-3 (1 nM) increased tyrosine phosphorylation of 120 Kda and 70 Kda astrocytic proteins [14].

Anatomical context of Edn3


Associations of Edn3 with chemical compounds


Regulatory relationships of Edn3


Other interactions of Edn3

  • Only Edn3 and Gnas did not recombine with the ls mutation [20].
  • The first phase of nociception (0-5 min after injection) was significantly potentiated by simultaneous injection of either ET-1 (10 or 30 pmol/paw) or ET-3 (10 pmol/paw), but not of the selective ET3 receptor agonist sarafotoxin S6c (SRTX-c; up to 30 pmol/paw) [2].
  • BQ-123 (a selective ETA receptor antagonist) inhibited the constrictive effects of ET-3 (not of ET-1) on the portal venules and central venules, whereas it had no inhibitory effect on the sinusoids [13].
  • Addition of the Kit ligand Mgf or endothelin 3 or a combination of these factors all rapidly increased the number of Dct-positive cells [21].
  • Most striking was the marked elevation of c-fos steady-state mRNA and protein by ET-1, as compared with ET-3 [22].

Analytical, diagnostic and therapeutic context of Edn3

  • Baroreflex sensitivity, which was calculated as the slope of the relationship between systolic BP and RR interval on an ECG, was also similar in ET-3 (-/-) mice (0.84+/-0.20 ms/mmHg) and wild-type mice (1.07+/-0.38 ms/mmHg) [23].
  • To investigate the possible involvement of ET-3 in central ventilatory control, we measured ventilation in mutant mice deficient in ET-3 by whole body plethysmography [24].
  • This article describes the development of an organ culture model using embryonic murine gut to determine how endothelin-3 regulates development of the enteric nervous system [25].
  • Using quantitative real-time polymerase chain reaction (PCR) we demonstrated reduced levels of endothelin converting enzyme-1 and endothelin-3 mRNA in the male mouse bowel at the time that ENS precursors migrate into the colon [26].
  • Characterization by reversed phase HPLC revealed, however, that a major portion of the neostriatal ET-3-like immunoreactivity was not identical to ET-3 [27].


  1. Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development. Stanchina, L., Baral, V., Robert, F., Pingault, V., Lemort, N., Pachnis, V., Goossens, M., Bondurand, N. Dev. Biol. (2006) [Pubmed]
  2. Endothelins potentiate formalin-induced nociception and paw edema in mice. Piovezan, A.P., D'Orléans-Juste, P., Tonussi, C.R., Rae, G.A. Can. J. Physiol. Pharmacol. (1997) [Pubmed]
  3. Endothelin and neural crest development. Kurihara, H., Kurihara, Y., Nagai, R., Yazaki, Y. Cell. Mol. Biol. (Noisy-le-grand) (1999) [Pubmed]
  4. Anti-ulcerogenic properties of endothelin receptor antagonists in the rat. Padol, I., Huang, J.Q., Hunt, R.H. Aliment. Pharmacol. Ther. (1999) [Pubmed]
  5. Central effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) in mice. Maslarova, J., Getova, D., Semkova, I., Nikolov, R. Methods and findings in experimental and clinical pharmacology. (1995) [Pubmed]
  6. A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome). Hofstra, R.M., Osinga, J., Tan-Sindhunata, G., Wu, Y., Kamsteeg, E.J., Stulp, R.P., van Ravenswaaij-Arts, C., Majoor-Krakauer, D., Angrist, M., Chakravarti, A., Meijers, C., Buys, C.H. Nat. Genet. (1996) [Pubmed]
  7. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Baynash, A.G., Hosoda, K., Giaid, A., Richardson, J.A., Emoto, N., Hammer, R.E., Yanagisawa, M. Cell (1994) [Pubmed]
  8. Ontogeny of endothelins-1 and -3, their receptors, and endothelin converting enzyme-1 in the early human embryo. Brand, M., Le Moullec, J.M., Corvol, P., Gasc, J.M. J. Clin. Invest. (1998) [Pubmed]
  9. Endothelin 3 selectively promotes survival and proliferation of neural crest-derived glial and melanocytic precursors in vitro. Lahav, R., Dupin, E., Lecoin, L., Glavieux, C., Champeval, D., Ziller, C., Le Douarin, N.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. Impaired growth and differentiation of diploid but not immortal melanoblasts from endothelin receptor B mutant (piebald) mice. Sviderskaya, E.V., Easty, D.J., Bennett, D.C. Dev. Dyn. (1998) [Pubmed]
  11. ET-1-induced bronchoconstriction is mediated via ETB receptor in mice. Nagase, T., Aoki, T., Oka, T., Fukuchi, Y., Ouchi, Y. J. Appl. Physiol. (1997) [Pubmed]
  12. A transformed murine Leydig cell line expresses the ETA receptor subtype. Ergul, A., Glassberg, M.K., Freeman, M.E., Puett, D. Mol. Cell. Biochem. (1994) [Pubmed]
  13. Constriction of mouse hepatic venules and sinusoids by endothelins through ETB receptor subtype. Ito, Y., Katori, M., Majima, M., Kakita, A. International journal of microcirculation, clinical and experimental / sponsored by the European Society for Microcirculation. (1996) [Pubmed]
  14. Endothelin-induced protein tyrosine phosphorylation of cultured astrocytes: its relationship to cytoskeletal actin organization. Koyama, Y., Baba, A. Glia (1999) [Pubmed]
  15. Endothelin-3 attenuates the cyclic GMP responses to C-type natriuretic peptide in cultured mouse astrocytes. Yeung, V.T., Ho, S.K., Tsang, D.S., Nicholls, M.G., Cockram, C.S. J. Neurosci. Res. (1996) [Pubmed]
  16. Development of melanocyte progenitors in murine Steel mutant neural crest explants cultured with stem cell factor, endothelin-3, or TPA. Ono, H., Kawa, Y., Asano, M., Ito, M., Takano, A., Kubota, Y., Matsumoto, J., Mizoguchi, M. Pigment Cell Res. (1998) [Pubmed]
  17. Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors. Wu, J.J., Chen, J.X., Rothman, T.P., Gershon, M.D. Development (1999) [Pubmed]
  18. Endothelin-elicited stimulation of phospholipase C is mediated by guanine nucleotide binding protein(s). Gusovsky, F. Eur. J. Pharmacol. (1992) [Pubmed]
  19. Evidence for atypical endothelin receptors and for presence of endothelin-converting enzyme activity in the mouse isolated vas deferens. Mass, J., D'Orléans-Juste, P., Yano, M., Rae, G.A. Eur. J. Pharmacol. (1995) [Pubmed]
  20. A high-resolution linkage map of the lethal spotting locus: a mouse model for Hirschsprung disease. Pavan, W.J., Liddell, R.A., Wright, A., Thibaudeau, G., Matteson, P.G., McHugh, K.M., Siracusa, L.D. Mamm. Genome (1995) [Pubmed]
  21. Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor. Opdecamp, K., Nakayama, A., Nguyen, M.T., Hodgkinson, C.A., Pavan, W.J., Arnheiter, H. Development (1997) [Pubmed]
  22. Differential regulation of fos and jun gene expression and AP-1 cis-element activity by endothelin isopeptides. Possible implications for mitogenic signaling by endothelin. Simonson, M.S., Jones, J.M., Dunn, M.J. J. Biol. Chem. (1992) [Pubmed]
  23. Blood pressure of endothelin-3 null (-/-) knockout mice and endothelin A receptor null (-/-) knockout mice under anaesthesia. Kuwaki, T., Ishii, T., Ju, K., Yanagisawa, M., Fukuda, Y. Clin. Sci. (2002) [Pubmed]
  24. Normal ventilation and ventilatory responses to chemical stimuli in juvenile mutant mice deficient in endothelin-3. Nakamura, A., Kuwaki, T., Kuriyama, T., Yanagisawa, M., Fukuda, Y. Respiration physiology. (2001) [Pubmed]
  25. Time-dependent effects of endothelin-3 on enteric nervous system development in an organ culture model of Hirschsprung's disease. Woodward, M.N., Kenny, S.E., Vaillant, C., Lloyd, D.A., Edgar, D.H. J. Pediatr. Surg. (2000) [Pubmed]
  26. Reduced endothelin converting enzyme-1 and endothelin-3 mRNA in the developing bowel of male mice may increase expressivity and penetrance of Hirschsprung disease-like distal intestinal aganglionosis. Vohra, B.P., Planer, W., Armon, J., Fu, M., Jain, S., Heuckeroth, R.O. Dev. Dyn. (2007) [Pubmed]
  27. Demonstration and nature of endothelin-3-like immunoreactivity in somatostatin and choline acetyltransferase-immunoreactive nerve cells of the neostriatum of the rat. Fuxe, K., Tinner, B., Staines, W., Hemsén, A., Hersh, L., Lundberg, J.M. Neurosci. Lett. (1991) [Pubmed]
WikiGenes - Universities