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Gene Review

Edn3  -  endothelin 3

Rattus norvegicus

Synonyms: ET-3, Endothelin-3, Et3, PPET3, Preproendothelin-3, ...
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Disease relevance of Edn3


Psychiatry related information on Edn3

  • The automated recording of motor activity revealed that, unlike ET (16-21), both ET-1 and ET-3 evoke a dose-regulated increase of the immobility time [5].
  • ET-3 (10 nM) showed the response time to peak pulmonary arterial pressure generation by hypoxia, the size of the response being unchanged [6].
  • We therefore examined the effects of endothelin-3 (ET-3) on ovulation and secretion of LH, FSH and prolactin in rats in which naturally occurring ovulation was blocked by the administration of sodium pentobarbital (40 mg/kg, i.p.) prior to the critical period (1330 h) on the day of pro-oestrus [7].

High impact information on Edn3

  • Loss of Endothelin-3/Endothelin receptor B (EDNRB) signaling leads to aganglionosis of the distal gut (Hirschsprung's disease), but it is unclear whether it is required primarily for neural crest progenitor maintenance or migration [8].
  • Interestingly, ET-3-induced skeletal alpha-actin gene expression and [3H]leucine incorporation were inhibited by a synthetic ETA receptor antagonist (BQ123) as well as by antisense oligonucleotides against peproET-1 mRNA [1].
  • BQ-123 had no effect on the response to ET-3 (10(-8) M) [9].
  • We conclude that ET-3 stimulates NO-induced cGMP generation through ETB receptor in glomerulus [10].
  • ETA receptor antagonist BQ123-Na did not inhibit ET-3- or IRL 1620-stimulated cGMP generation [10].

Chemical compound and disease context of Edn3


Biological context of Edn3


Anatomical context of Edn3


Associations of Edn3 with chemical compounds


Physical interactions of Edn3

  • The three monoiodo ET-3 derivatives bound to recombinant rat ETB receptors with a pM affinity [23].
  • 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 [24].
  • Furthermore, ET-3 binding in the inner medulla could be blocked with an ETA receptor antagonist in sl/sl rats but not in tissue from sl/+ rats [25].

Regulatory relationships of Edn3

  • Compared with ET-1, ET-3 stimulated only a rapid increase of p42 MAP kinase activity [26].
  • ET-3-induced ICAM-1 expression on endothelial cells was inhibited by BQ788 but not by S-0139 [27].
  • Although ET-3 also activates ETA receptors in smooth muscle to induce contraction, this effect is overcome by the relaxant effect mediated by ETB receptors [28].
  • These results indicate that the anterior pituitary cells secrete ET-3 and the secretion is stimulated by IGF-I [29].
  • On the other hand, injection of C3 enzyme did not affect increase in cytoplasmic Ca2+ levels induced by ET-3 [30].

Other interactions of Edn3

  • The increases in ECE-1, ET-1, and ET-3 and their receptor expression after balloon angioplasty suggest that these proteins play an active role in the pathogenesis of neointimal formation [31].
  • [125I]Et-1 binding experiments showed the presence in rat brain capillary endothelial cells of typical ETA receptors that recognized Et-1, BQ-123 and FR139317 but not IRL1620, [Ala1,3.11,15]ET-1 or Et-3 [22].
  • ET-3-induced [3H]leucine incorporation, skeletal alpha-actin mRNA and cell surface area were inhibited by a synthetic ETB receptor antagonist (BQ788) [1].
  • ET-3 (10(-9)-10(-7) M) increased mRNA level for skeletal alpha-actin with a maximum response after 6 h [1].

Analytical, diagnostic and therapeutic context of Edn3

  • Since the response of cardiac hypertrophy is characterized by enhanced expression of fetal isoforms of muscle specific genes, the effect of ET-3 on steady state levels of mRNA for skeletal alpha-actin was evaluated by Northern blot analysis [1].
  • A similarly delayed increase in preproET-3 mRNA was observed at 7 days (2.8-fold increase, P < .05) and 14 days (2.6-fold increase, P < .05) after angioplasty [31].
  • ET-1 (EC50 = 1.5 x 10(-10) M) and endothelin-3 (ET-3) (10(-11)-3 x 10(-8) M) caused dose-dependent increases in coronary perfusion pressure [32].
  • Immunohistochemical distribution of ET-1 and ET-3, ligand binding, and autoradiography to determine ET receptor distribution were carried out [33].
  • When either ET-1 or ET-3 was administered to the rat striatum via a microinjection needle, the dopamine release from the striatum dose-dependently increased [34].


  1. 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]
  2. BQ-123 inhibits both endothelin 1 and endothelin 3 mediated C6 rat glioma cell proliferation suggesting an atypical endothelin receptor. Sedo, n.u.l.l., Provero, P., Revoltella, R.P., Di Bartolo, V., Beffy, P., Mizrahi, J. J. Biol. Regul. Homeost. Agents (1993) [Pubmed]
  3. Regulation of endothelin-converting enzyme 1 in nephrotic syndrome in rats. Ikebe, M., Nonoguchi, H., Nakayama, Y., Tashima, Y., Shimada, K., Tanzawa, K., Tomita, K. Nephron Exp. Nephrol. (2003) [Pubmed]
  4. cGMP formation in rat atrial slices is ligand and endothelin receptor subtype specific. Shraga-Levine, Z., Sokolovsky, M. Circ. Res. (1996) [Pubmed]
  5. 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]
  6. Endothelin-3 is a potent pulmonary vasodilator in the rat. Crawley, D.E., Liu, S.F., Barnes, P.J., Evans, T.W. J. Appl. Physiol. (1992) [Pubmed]
  7. Induction of ovulation by endothelin-3 in rats. Furudate, S., Masaki, Y., Muto, T. J. Endocrinol. (1994) [Pubmed]
  8. Temporally distinct requirements for endothelin receptor B in the generation and migration of gut neural crest stem cells. Kruger, G.M., Mosher, J.T., Tsai, Y.H., Yeager, K.J., Iwashita, T., Gariepy, C.E., Morrison, S.J. Neuron (2003) [Pubmed]
  9. Prostaglandin E2 abrogates endothelin-induced vasoconstriction in renal outer medullary descending vasa recta of the rat. Silldorff, E.P., Yang, S., Pallone, T.L. J. Clin. Invest. (1995) [Pubmed]
  10. 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]
  11. Dysfunctional renal nitric oxide synthase as a determinant of salt-sensitive hypertension: mechanisms of renal artery endothelial dysfunction and role of endothelin for vascular hypertrophyandGlomerulosclerosis. Barton, M., Vos, I., Shaw, S., Boer, P., D'Uscio, L.V., Gröne, H.J., Rabelink, T.J., Lattmann, T., Moreau, P., Lüscher, T.F. J. Am. Soc. Nephrol. (2000) [Pubmed]
  12. Effects of hypoxia on growth factor expression in the rat kidney in vivo. Krämer, B.K., Bucher, M., Sandner, P., Ittner, K.P., Riegger, G.A., Ritthaler, T., Kurtz, A. Kidney Int. (1997) [Pubmed]
  13. Altered microvascular reactivity to endothelin-1, endothelin-3 and NG-nitro-L-arginine methyl ester in streptozotocin-induced diabetes mellitus. Lawrence, E., Brain, S.D. Br. J. Pharmacol. (1992) [Pubmed]
  14. 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]
  15. Endothelin-1 and endothelin-3 induce chemotaxis and replication of pulmonary artery fibroblasts. Peacock, A.J., Dawes, K.E., Shock, A., Gray, A.J., Reeves, J.T., Laurent, G.J. Am. J. Respir. Cell Mol. Biol. (1992) [Pubmed]
  16. Influence of endothelins and sarafotoxin 6c and L-NAME on renal vasoconstriction in the anaesthetized rat. Marshall, J.L., Johns, E.J. Br. J. Pharmacol. (1999) [Pubmed]
  17. Behavioural, autonomic and endocrine responses associated with C-fos expression in the forebrain and brainstem after intracerebroventricular infusions of endothelins. Zhu, B., Herbert, J. Neuroscience (1996) [Pubmed]
  18. 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]
  19. Role of endothelin in mediating neurogenic plasma extravasation in rat dura mater. Brändli, P., Löffler, B.M., Breu, V., Osterwalder, R., Maire, J.P., Clozel, M. Pain (1996) [Pubmed]
  20. Endothelin expression in ocular tissues of diabetic and insulin-treated rats. Chakravarthy, U., Hayes, R.G., Stitt, A.W., Douglas, A. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  21. Endothelins stimulate cyclic AMP accumulation in the isolated rat anterior pituitary gland: possible involvement of ETA receptor activation and prostaglandin E2 production. Domae, M., Yamada, K., Inoue, T., Satoh, M., Furukawa, T. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  22. Properties of an endothelin-3-sensitive Eta-like endothelin receptor in brain capillary endothelial cells. Vigne, P., Desmarets, J., Guedin, D., Frelin, C. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  23. High affinity interaction of endothelin-3 with recombinant ETA receptors. Desmarets, J., Frelin, C. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  24. 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]
  25. Unique endothelin receptor binding in kidneys of ETB receptor deficient rats. Taylor, T.A., Gariepy, C.E., Pollock, D.M., Pollock, J.S. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  26. 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]
  27. ICAM-1 expression on cardiac myocytes and aortic endothelial cells via their specific endothelin receptor subtype. Hayasaki, Y., Nakajima, M., Kitano, Y., Iwasaki, T., Shimamura, T., Iwaki, K. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  28. Effect of endothelin-3 on cytosolic calcium level in vascular endothelium and on smooth muscle contraction. Sudjarwo, S.A., Hori, M., Karaki, H. Eur. J. Pharmacol. (1992) [Pubmed]
  29. Insulin-like growth factor-I stimulates endothelin-3 secretion from rat anterior pituitary cells in primary culture. Matsumoto, H., Suzuki, N., Shiota, K., Inoue, K., Tsuda, M., Fujino, M. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  30. Endothelin-induced cytoskeletal actin re-organization in cultured astrocytes: inhibition by C3 ADP-ribosyltransferase. Koyama, Y., Baba, A. Glia (1996) [Pubmed]
  31. Expression of endothelin-1, endothelin-3, endothelin-converting enzyme-1, and endothelin-A and endothelin-B receptor mRNA after angioplasty-induced neointimal formation in the rat. Wang, X., Douglas, S.A., Louden, C., Vickery-Clark, L.M., Feuerstein, G.Z., Ohlstein, E.H. Circ. Res. (1996) [Pubmed]
  32. Two subtypes of the endothelin receptor (ETA and ETB) mediate vasoconstriction in the perfused rat heart. Balwierczak, J.L. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
  33. Endothelins, their receptors, and retinal vascular dysfunction in galactose-fed rats. Evans, T., Xi Deng, D., Mukherjee, K., Downey, D., Chakrabarti, S. Diabetes Res. Clin. Pract. (2000) [Pubmed]
  34. Endothelin-1 and endothelin-3 modulate dopaminergic neurons through different mechanisms. Horie, K., Morita, A., Yokogoshi, H. Life Sci. (1995) [Pubmed]
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