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Gene Review

Edn2  -  endothelin 2

Rattus norvegicus

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

  • Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells through regulation of endothelin-2/vasoactive intestinal contractor [1].
  • We isolated two proteins, ET-1 and ET-2, from the sporangial extracts of Clostridium perfringens type A. Both proteins had some properties in common with the well-known C. perfringens enterotoxin [2].
  • In isolated stimulated rat atria, superfusion with veratrine caused a marked contracture (VIC) which was absent in calcium-free medium and which was inhibited by tetrodotoxin (IC50VIC of 1.38 microM) [3].
  • ET-1, ET-2, ET-3 and sarafotoxin S6b (STX) induced rhythmic contractions superimposed on an increased muscle tone [4].
  • ET-2 promoter, which is the 5'-flanking region of preproET-2 gene (5'ET-2), showed a marked increase in luciferase activity during acute hypoxia [5].

High impact information on Edn2

  • We found that the gene coding for endothelin-2 (ET2), also known as vasoctive intestine peptide, cosegregated strongly with systolic blood pressure in a F2 population [F2(S x LEW)] derived from a cross of the Dahl salt-sensitive (S) rat and the Lewis (LEW/NCrlBR) (LEW) rat [6].
  • The ET2 locus was assigned to rat chromosome 5 [6].
  • We conclude that, in the rat, one new blood pressure QTL is located on chromosome 5 marked by the ET2 locus and another new QTL is located on chromosome 17 near the HITH locus [6].
  • Endothelin (ET)-3 dose-dependently stimulated cGMP accumulation in glomerulus, which was higher than that of ET-1 or ET-2 [7].
  • ET2 was expressed at high level in both large and small intestine and at low level in stomach, muscle, and heart, but ET2 mRNA could not be detected elsewhere [8].

Chemical compound and disease context of Edn2


Biological context of Edn2


Anatomical context of Edn2


Associations of Edn2 with chemical compounds

  • In contrast, bosentan delayed the rate of onset, and reduced the duration, of the mesenteric vasoconstrictor actions of ET-2 and ET-3 [18].
  • Intracerebroventricular injection of 6, 12, and 20 ng ET-2 resulted in a significant, dose-related inhibition of water drinking in response to subsequent injection of 100 pmol angiotensin II (ANG II) [19].
  • The fibres contracted in response to treatment with KCl (80 mM), ACh (100 microM), endothelin-1 (10 nM), endothelin-2 (10 nM), and prostaglandin F2alpha (100 microM) [20].
  • PRL release inhibition by VIC was not mediated via the D2-dopamine receptor and was not prevented by calcium channel blockade with 100 nM nifedipine [21].
  • ET-2 was the more anionic protein since it eluted more slowly from the anion exchange column and migrated faster toward the anode in polyacrylamide disk gel electrophoresis (pH 8.5, native gels) [2].

Analytical, diagnostic and therapeutic context of Edn2

  • RT-PCR analysis, morphological observations, and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 200 microM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced neurite outgrowth in PC-12 rat pheochromocytoma cells [1].
  • Both ET-1 and ET-2 showed lines of identity in agar gel double immunodiffusion against anti-enterotoxin antiserum [2].
  • 1. The response of the cutaneous microvasculature to intradermal injection of the endothelins (ET-1, ET-2 and ET-3) and the modulatory effect of endogenously produced nitric oxide (NO) have been determined in the rat [22].
  • The influence of endothelin on vascular and myocardial reperfusion damage was studied with exogenous endothelin-2 [23].
  • After 1 h of low-flow ischaemia, endothelin-2 increased the coronary perfusion pressure to a similar extent as in non-ischaemic hearts, but with a 30-times higher potency [23].


  1. Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells through regulation of endothelin-2/vasoactive intestinal contractor. Kotake-Nara, E., Takizawa, S., Quan, J., Wang, H., Saida, K. J. Neurosci. Res. (2005) [Pubmed]
  2. Purification of two Clostridium perfringens enterotoxin-like proteins and their effects on membrane permeability in primary cultures of adult rat hepatocytes. Dasgupta, B.R., Pariza, M.W. Infect. Immun. (1982) [Pubmed]
  3. Protective effect of bepridil against veratrine-induced contracture in rat atria. Leboeuf, J., Baissat, J., Massingham, R. Eur. J. Pharmacol. (1992) [Pubmed]
  4. Effects of endothelin on cytosolic Ca2+ level and mechanical activity in rat uterine smooth muscle. Sakata, K., Karaki, H. Eur. J. Pharmacol. (1992) [Pubmed]
  5. Myocardial expression of endothelin-2 is altered reciprocally to that of endothelin-1 during ischemia of cardiomyocytes in vitro and during heart failure in vivo. Kakinuma, Y., Miyauchi, T., Kobayashi, T., Yuki, K., Maeda, S., Sakai, S., Goto, K., Yamaguchi, I. Life Sci. (1999) [Pubmed]
  6. Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes. Deng, A.Y., Dene, H., Pravenec, M., Rapp, J.P. J. Clin. Invest. (1994) [Pubmed]
  7. 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]
  8. Organ distribution of the three rat endothelin messenger RNAs and the effects of ischemia on renal gene expression. Firth, J.D., Ratcliffe, P.J. J. Clin. Invest. (1992) [Pubmed]
  9. Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia. Gulati, A. Life Sci. (1992) [Pubmed]
  10. Property of receptor for vasoactive intestinal contractor (VIC) expressed in Xenopus oocytes injected with mRNA from rat intestine. Yoshimura, M., Yoshida, S., Taniyama, K. Life Sci. (1996) [Pubmed]
  11. Effect of centrally administered endothelin agonists on systemic and regional blood circulation in the rat: role of sympathetic nervous system. Gulati, A., Kumar, A., Morrison, S., Shahani, B.T. Neuropeptides (1997) [Pubmed]
  12. Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor. Lin, H.Y., Kaji, E.H., Winkel, G.K., Ives, H.E., Lodish, H.F. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  13. Ca2+ signaling by distinct endothelin peptides in glomerular mesangial cells. Simonson, M.S., Dunn, M.J. Exp. Cell Res. (1991) [Pubmed]
  14. Immunocytochemical studies on endothelin in mast cells and macrophages in the rat gastrointestinal tract. Liu, Y., Yamada, H., Ochi, J. Histochem. Cell Biol. (1998) [Pubmed]
  15. [125I]BQ3020, a novel endothelin agonist selective for the endothelinB receptor subtype. Assal, A.A., Gessner, G., Jarvis, M.F. Brain Res. Brain Res. Protoc. (1997) [Pubmed]
  16. Heterogeneity of cell surface endothelin receptors. Martin, E.R., Brenner, B.M., Ballermann, B.J. J. Biol. Chem. (1990) [Pubmed]
  17. Potent constrictor actions of endothelin-1, endothelin-2, and endothelin-3 in rat isolated portal vein. Guimarães, C.L., Calixto, J.B., Rae, G.A. Hypertension (1992) [Pubmed]
  18. Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats. Gardiner, S.M., Kemp, P.A., March, J.E., Bennett, T. Br. J. Pharmacol. (1994) [Pubmed]
  19. Antidipsogenic actions of endothelins are exerted via the endothelin-A receptor in the brain. Samson, W.K., Murphy, T.C. Am. J. Physiol. (1993) [Pubmed]
  20. Contractile responses of smooth muscle cells differentiated from rat neural stem cells. Oishi, K., Ogawa, Y., Gamoh, S., Uchida, M.K. J. Physiol. (Lond.) (2002) [Pubmed]
  21. Comparison of the pituitary effects of the mammalian endothelins: vasoactive intestinal contractor (endothelin-beta, rat endothelin-2) is a potent inhibitor of prolactin secretion. Samson, W.K., Skala, K.D. Endocrinology (1992) [Pubmed]
  22. Responses to endothelins in the rat cutaneous microvasculature: a modulatory role of locally-produced nitric oxide. Lawrence, E., Brain, S.D. Br. J. Pharmacol. (1992) [Pubmed]
  23. Endothelin release during ischaemia and reperfusion of isolated perfused rat hearts. Brunner, F., du Toit, E.F., Opie, L.H. J. Mol. Cell. Cardiol. (1992) [Pubmed]
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