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Gene Review

Ednra  -  endothelin receptor type A

Rattus norvegicus

Synonyms: ET-A, ET-AR, Endor, Endothelin A receptor, Endothelin-1 receptor, ...
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Disease relevance of Ednra

  • In addition, the tissue concentration of endothelin and endothelin 1 messenger RNA (mRNA) and the effect of an endothelin A receptor antagonist on arterial and portal pressure were assessed in cirrhotic rats with ascites and control rats [1].
  • The role of ETB receptors in mediating inflammation was evidenced by the lack of efficacy of a selective ETA receptor antagonist, in contrast to the full efficacy of a selective ETB receptor antagonist, for preventing neurogenic inflammation induced by unilateral stimulation of the trigeminal ganglion [2].
  • The results suggest that endothelins increase cAMP levels via ETA receptor activation interacting with the pertussis toxin-insensitive G-protein, in which PGE2 production is involved in the rat anterior pituitary, whereas endothelins lack these effects in the intermediate-posterior pituitary [3].
  • The ETA receptor density was significantly elevated, whereas the density of the ETB receptor was decreased in Morris hepatoma 7777 [4].
  • These data indicate that ET-1 interacts with both ETA and ETB receptors to elicit calcium transients in UMR-106 osteoblastic osteosarcoma cells [5].

High impact information on Ednra

  • Indeed, blockade of ETA endothelin receptors with BQ-610 (1 microM), similar to removal of the endothelium and alpha5 integrin blockade, inhibited the vasoconstriction [6].
  • 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 [7].
  • Stellate cells possess abundant endothelin (ET) receptors (ETA/B) and, therefore, are subject to the effects of ET-1 and 3 [8].
  • Furthermore, the mixed ETA/B receptor antagonist, bosentan, blocked this process [8].
  • Since ETA receptor mRNA is increased under hyperosmolar conditions, we conclude that ET receptor downregulation is the consequence of either decreased translation of message, increased degradation of receptor peptide, or increased internalization of specific receptor sites [9].

Chemical compound and disease context of Ednra


Biological context of Ednra


Anatomical context of Ednra


Associations of Ednra with chemical compounds

  • METHODS: Male Sprague-Dawley rats were continuously infused with 2.5 mL/h of saline, 0.8 mg . kg-1 . h-1 of lipopolysaccharide (LPS), 3 mg . kg-1 . h-1 of BQ-485, an endothelin A-receptor antagonist, or LPS plus BQ-485 for 7 hours [22].
  • Secretion of the natriuretic peptides was blocked by BQ-123, an ETA-receptor antagonist, but was not affected by either IRL-1620 or [Ala1,3,11,15]ET-1, two ETB-receptor agonists [15].
  • Regulation of endothelin-A receptor sensitivity by cyclic adenosine monophosphate in rat hepatic stellate cells [23].
  • Rats were fed a K(+)-deficient diet alone (LC) or with an ETA-selective antagonist ABT-627 (LA) or an ETB-selective antagonist A-192621 (LB) for 8 wk [24].
  • These increases were followed by decreased expression of ECE-1, ET A-type receptor, and ET B-type receptor mRNA at 6 h after injection, and serum creatinine levels were increased at 24 h after CsA injection [25].

Physical interactions of Ednra

  • 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 [26].
  • Collectively, these findings suggest that ETs can regulate vascular tone in the in situ perfused rat adrenals via both PKC-coupled ETA and NOS-coupled ETB receptors, the activation of which evokes vasoconstriction and vasodilation, respectively [27].

Regulatory relationships of Ednra

  • ETA blockade significantly ameliorated all parameters for renal injury in the cortex without suppressing local ET-1 and ETA expression [24].
  • Moreover, the LPS inhibitory effect of on mucin synthesis was blocked by ETA receptor antagonist, BQ610, but not by ETB receptor antagonist, BQ788 [28].
  • 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 [29].
  • Thus, ET-1 contracts rat pulmonary artery and aorta predominantly via ETA receptors (responses blocked by BQ-123) and functional ETB receptors are unlikely to be present (no responses to IRL 1620) [30].
  • Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes [31].

Other interactions of Ednra


Analytical, diagnostic and therapeutic context of Ednra

  • The levels of ETA receptor mRNA were elevated 29.3-fold (P < .001) and 24.3-fold (P < .01) at 3 and 7 days, respectively, after angioplasty [35].
  • Northern blot analysis of both ETA- and ETB-receptor mRNAs allowed only the detection of the former, indicating that the ETB receptor may be expressed in very small amounts [15].
  • Moreover, the ETA receptor and downstream effector phospholipase C-beta 1 were co-localized within T-tubules using standard immunofluorescence techniques, and protein kinase C (PKC)-epsilon-enhanced green fluorescent protein bound reversibly to T-tubules upon activation [20].
  • Retrograde perfusion suggests that ETB receptors are located arterially whereas ETA receptors are predominantly venous in distribution.(ABSTRACT TRUNCATED AT 250 WORDS)[36]
  • Castration does not cause significant changes in the pharmacological properties of prostatic ET receptors, i.e., the predominance of ETA receptors in either region of the prostate, or the expression of ETA receptor subtype mRNA in the ventral region of the castrated rat prostate [37].


  1. Endothelin 1 does not play a major role in the homeostasis of arterial pressure in cirrhotic rats with ascites. Leivas, A., Jiménez, W., Lamas, S., Bosch-Marcé, M., Oriola, J., Clària, J., Arroyo, V., Rivera, F., Rodés, J. Gastroenterology (1995) [Pubmed]
  2. 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]
  3. 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]
  4. The endothelin system in Morris hepatoma-7777: an endothelin receptor antagonist inhibits growth in vitro and in vivo. Pfab, T., Stoltenburg-Didinger, G., Trautner, C., Godes, M., Bauer, C., Hocher, B. Br. J. Pharmacol. (2004) [Pubmed]
  5. Endothelin-1-evoked calcium transients in UMR-106 osteoblastic osteosarcoma cells are mediated through endothelin-A and endothelin-B receptors. Semler, D.E., Ohlstein, E.H., Nambi, P., Slater, C., Stern, P.H. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  6. RGDN peptide interaction with endothelial alpha5beta1 integrin causes sustained endothelin-dependent vasoconstriction of rat skeletal muscle arterioles. Mogford, J.E., Davis, G.E., Meininger, G.A. J. Clin. Invest. (1997) [Pubmed]
  7. 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]
  8. Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. Rockey, D.C., Chung, J.J. J. Clin. Invest. (1996) [Pubmed]
  9. Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells. Vernace, M.A., Mento, P.F., Maita, M.E., Girardi, E.P., Chang, M.D., Nord, E.P., Wilkes, B.M. J. Clin. Invest. (1995) [Pubmed]
  10. Role of endothelin-1/endothelin receptor system in endotoxic shock rats. Ishimaru, S., Shichiri, M., Mineshita, S., Hirata, Y. Hypertens. Res. (2001) [Pubmed]
  11. The role of atrial natriuretic peptide and endothelin in hypoxia induced pulmonary hypertension. Chen, Y.F., Li, H., Elton, T.S., Yang, R.H., Jin, H., Oparil, S. The Chinese journal of physiology. (1994) [Pubmed]
  12. 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]
  13. Inotropic effects of endothelin-1: interaction with molsidomine and with BQ 610. Beyer, M.E., Slesak, G., Hövelborn, T., Kazmaier, S., Nerz, S., Hoffmeister, H.M. Hypertension (1999) [Pubmed]
  14. Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation. Ergul, A., Portik-Dobos, V., Giulumian, A.D., Molero, M.M., Fuchs, L.C. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  15. 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]
  16. Coupling of endothelin B receptors to the calcium pump and phospholipase C via Gs and Gq in rat liver. Jouneaux, C., Mallat, A., Serradeil-Le Gal, C., Goldsmith, P., Hanoune, J., Lotersztajn, S. J. Biol. Chem. (1994) [Pubmed]
  17. Endothelin receptor type A signals both the accumulation of inositol phosphates and the inhibition of cyclic AMP generation in rat myometrium: stimulation and desensitization. Khac, L.D., Naze, S., Harbon, S. Mol. Pharmacol. (1994) [Pubmed]
  18. Endothelin B receptor-mediated vasoconstriction induced by endothelin A receptor antagonist. Zhang, Y., Oliver, J.R., Horowitz, J.D. Cardiovasc. Res. (1998) [Pubmed]
  19. 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]
  20. Localization of functional endothelin receptor signaling complexes in cardiac transverse tubules. Robu, V.G., Pfeiffer, E.S., Robia, S.L., Balijepalli, R.C., Pi, Y., Kamp, T.J., Walker, J.W. J. Biol. Chem. (2003) [Pubmed]
  21. 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]
  22. Endothelin A-receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis. Nishida, T., Huang, T.P., Seiyama, A., Hamada, E., Kamiike, W., Ueshima, S., Kazuo, H., Matsuda, H. Gastroenterology (1998) [Pubmed]
  23. Regulation of endothelin-A receptor sensitivity by cyclic adenosine monophosphate in rat hepatic stellate cells. Reinehr, R., Fischer, R., Häussinger, D. Hepatology (2002) [Pubmed]
  24. Endothelin a receptor blockade and endothelin B receptor blockade improve hypokalemic nephropathy by different mechanisms. Suga, S., Yasui, N., Yoshihara, F., Horio, T., Kawano, Y., Kangawa, K., Johnson, R.J. J. Am. Soc. Nephrol. (2003) [Pubmed]
  25. Intranephron distribution and regulation of endothelin-converting enzyme-1 in cyclosporin A-induced acute renal failure in rats. Nakayama, Y., Nonoguchi, H., Kiyama, S., Ikebe, M., Tashima, Y., Shimada, K., Tanzawa, K., Tomita, K. J. Am. Soc. Nephrol. (1999) [Pubmed]
  26. 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]
  27. Role of endothelins in regulation of vascular tone in the in situ perfused rat adrenals. Mazzocchi, G., Malendowicz, L.K., Musajo, F.G., Gottardo, G., Markowska, A., Nussdorfer, G.G. Am. J. Physiol. (1998) [Pubmed]
  28. Porphyromonas gingivalis lipopolysaccharide-induced up-regulation in endothelin-1 interferes with salivary mucin synthesis via epidermal growth factor receptor transactivation. Slomiany, B.L., Slomiany, A. IUBMB Life (2004) [Pubmed]
  29. 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]
  30. Effects of endothelin receptor selective antagonists, BQ-123 and BQ-788, on IRL 1620 and endothelin-1 responses of airway and vascular preparations from rats. O'Donnell, S.R., Kay, C.S. Pulmonary pharmacology. (1995) [Pubmed]
  31. Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes. Caligiuri, A., Glaser, S., Rodgers, R.E., Phinizy, J.L., Robertson, W., Papa, E., Pinzani, M., Alpini, G. Am. J. Physiol. (1998) [Pubmed]
  32. 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]
  33. Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in rats. De Smet, H.R., Menadue, M.F., Oliver, J.R., Phillips, P.A. Clin. Exp. Pharmacol. Physiol. (2003) [Pubmed]
  34. Endothelin A receptor blockade decreases expression of growth factors and collagen and improves matrix metalloproteinase-2 activity in kidneys from stroke-prone spontaneously hypertensive rats. Tostes, R.C., Touyz, R.M., He, G., Ammarguellat, F., Schiffrin, E.L. J. Cardiovasc. Pharmacol. (2002) [Pubmed]
  35. 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]
  36. Actions of endothelins and sarafotoxin 6c in the rat isolated perfused lung. Lal, H., Woodward, B., Williams, K.I. Br. J. Pharmacol. (1995) [Pubmed]
  37. The effect of castration on endothelins, their receptors and endothelin converting enzyme in rat prostate. Takahashi, W., Afiatpour, P., Jr Foster, H.E., Ikeda, K., Wada, Y., Weiss, R.M., Latifpour, J. Naunyn Schmiedebergs Arch. Pharmacol. (2002) [Pubmed]
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