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Gene Review

EDNRA  -  endothelin receptor type A

Ovis aries

Synonyms: ETAR, eta
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Disease relevance of ETAR


High impact information on ETAR

  • To determine the potential contribution of endothelin (ET) to modulation of high pulmonary vascular resistance in the normal fetus, we studied the effects of BQ 123, a selective ET-A receptor antagonist, and sarafoxotoxin S6c (SFX), a selective ET-B receptor agonist, in 31 chronically prepared late gestation fetal lambs [5].
  • To determine whether big-endothelin-1 (big-ET-1)-induced pulmonary vasoconstriction is mediated by ET-A receptor stimulation, we studied the effects of big-ET-1 with or without pretreatment with BQ 123 [5].
  • We conclude that: (a) BQ 123 causes sustained fetal pulmonary vasodilation, but did not change vascular resistance in the fetal hindlimb; (b) Big-ET-1-induced pulmonary vasoconstriction may be mediated through ET-A receptor stimulation; and (c) ET-B receptor stimulation causes pulmonary vasodilation through EDNO release [5].
  • The purpose of this study was to determine (1) the effect of aerosolized ET-1 on tracheal mucus velocity (TMV), a marker of mucociliary clearance, in sheep and (2) if the ET-1-induced effects were mediated by ET-A or ET-B receptors [6].
  • Before and after shunt opening, lambs received an infusion of saline (n = 9), tezosentan, an ETA- and ETB -receptor antagonist (n = 6), or Nomega-nitro-L-arginine (L-NNA), a NO synthase (NOS) inhibitor (n = 5) [7].

Chemical compound and disease context of ETAR

  • METHODS AND RESULTS: We measured plasma ET-1 concentrations by radioimmunoassay in isolated blood-perfused neonatal lamb hearts before and after 2 hours of 10 degrees C cardioplegic ischemia and examined the effects of ET-1 and the endothelin-A (ET-A) receptor antagonist BE-18257B on the postischemic recovery of isolated hearts [2].

Biological context of ETAR


Anatomical context of ETAR

  • In the current study, isometric tension recording and radioligand binding techniques were used to characterize the ETA receptor population in sheep isolated tracheal smooth muscle [10].
  • We examined gene and surface expression and activity of the endothelin (ET)-1 receptors (ETA and ETB) in subendothelial (L1) and inner medial (L2) cells from the main pulmonary artery of sheep with continuous air embolization (CAE)-induced chronic pulmonary hypertension (CPH) [11].
  • The inhibitory effect of the endothelium was reversed by the Endothelin-A receptor (ET-A) antagonist BQ 123 (p < 0.01) [12].
  • In summary, ETA-receptor blockade and ET-1-converting enzyme inhibition augment and prolong fetal pulmonary vasodilation during partial compression of the ductus arteriosus [13].
  • In addition to mapping the distribution of ET receptors in sheep choroid plexus, our results strongly suggest that ET-1 binding to the ETA receptor leads to dimer formation [14].

Associations of ETAR with chemical compounds

  • The endothelin A receptor antagonists PD 156707 (CI-1020) and PD 180988 (CI-1034) reverse the hypoxic pulmonary vasoconstriction in the perinatal lamb [15].
  • Treatment with ETA (BQ-610) and ETB (BQ-788) receptor antagonists demonstrated that both receptors contributed to internalization of ET-1 in control L2 cells, whereas in hypertensive cells only when both receptor antagonists were used in combination was significant suppression of ET-1 internalization found [11].
  • The ETA receptor-selective antagonists BQ-123 and FR139317 caused concentration-dependent inhibition of the contractions induced by endothelin-1 and sarafotoxin S6b, but both antagonists were significantly less potent in inhibiting contractions induced by endothelin-1 than sarafotoxin S6b [10].
  • 1. The relative roles of ETA and ETB receptor activation on cholinergic nerve-mediated contraction and acetylcholine (ACh) release were examined in sheep isolated tracheal smooth muscle [16].
  • We studied the hemodynamic effects of two ET-1 antagonists, BQ-123 (a selective ETA-receptor antagonist) and phosphoramidon (a nonselective ET-1-converting enzyme inhibitor) during mechanical increases in pressure due to partial ductus arteriosus compression in chronically prepared late-gestation fetal lambs [13].

Regulatory relationships of ETAR


Other interactions of ETAR

  • This study demonstrates that ETa receptor activation has a small role in maintaining basal fetal pulmonary vascular tone, and that specific ETb receptor activation produces marked pulmonary vasodilation [18].

Analytical, diagnostic and therapeutic context of ETAR


  1. Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure. Fratz, S., Meyrick, B., Ovadia, B., Johengen, M.J., Reinhartz, O., Azakie, A., Ross, G., Fitzgerald, R., Oishi, P., Hess, J., Black, S.M., Fineman, J.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  2. Effects of endothelin-1 and endothelin-A receptor antagonist on recovery after hypothermic cardioplegic ischemia in neonatal lamb hearts. Hiramatsu, T., Forbess, J., Miura, T., Roth, S.J., Cioffi, M.A., Mayer, J.E. Circulation (1995) [Pubmed]
  3. Effect of Ro 61-1790, a selective endothelin-A receptor antagonist, on systemic and uterine hemodynamics and fetal oxygenation in sheep. McElvy, S., Greenberg, S., Baker, R.S., Khoury, J., Clark, K.E. Am. J. Obstet. Gynecol. (2002) [Pubmed]
  4. The endothelin-A-receptor antagonist PD 180988 (CI-1034) selectively reverses the pulmonary vasoconstrictor response to hypoxia in the lamb. Coe, Y., Haleen, S.J., Welch, K.M., Coceani, F. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
  5. Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation. Ivy, D.D., Kinsella, J.P., Abman, S.H. J. Clin. Invest. (1994) [Pubmed]
  6. Endothelin-1 depresses tracheal mucus velocity in ovine airways via ET-A receptors. Sabater, J.R., Otero, R., Abraham, W.M., Wanner, A., O'Riordan, T.G. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  7. Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs. Oishi, P., Azakie, A., Harmon, C., Fitzgerald, R.K., Grobe, A., Xu, J., Hendricks-Munoz, K., Black, S.M., Fineman, J.R. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  8. Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow. Petrossian, E., Parry, A.J., Reddy, V.M., Akkersdijk, G.P., McMullan, D.M., Thompson, L., Hendricks-Munoz, K.D., Hallak, H., Hanley, F.L., Fineman, J.R. J. Thorac. Cardiovasc. Surg. (1999) [Pubmed]
  9. Characterization of endothelin receptor subtypes on airway smooth muscle cells. Ergul, A., Glassberg, M.K., Wanner, A., Puett, D. Exp. Lung Res. (1995) [Pubmed]
  10. Typical endothelin ETA receptors mediate atypical endothelin-1-induced contractions in sheep isolated tracheal smooth muscle. Henry, P.J., King, S.H. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  11. ET-1 receptor gene expression and distribution in L1 and L2 cells from hypertensive sheep pulmonary artery. Balyakina, E.V., Chen, D., Lawrence, M.L., Manning, S., Parker, R.E., Shappell, S.B., Meyrick, B. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  12. Interaction of KATP channels and endothelin-1 in lambs with persistent pulmonary hypertension of the newborn. Maurey, C., Hislop, A.A., Advenier, C., Vouhé, P.R., Israël-Biet, D., Lévy, M. Pediatr. Res. (2006) [Pubmed]
  13. Endothelin blockade augments pulmonary vasodilation in the ovine fetus. Ivy, D.D., Kinsella, J.P., Abman, S.H. J. Appl. Physiol. (1996) [Pubmed]
  14. Identification of endothelin receptor subtypes in sheep choroid plexus. Angelova, K., Puett, D., Narayan, P. Endocrine (1997) [Pubmed]
  15. The endothelin A receptor antagonists PD 156707 (CI-1020) and PD 180988 (CI-1034) reverse the hypoxic pulmonary vasoconstriction in the perinatal lamb. Coe, Y., Haleen, S.J., Welch, K.M., Liu, Y.A., Coceani, F. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  16. Inhibition by endothelin-1 of cholinergic nerve-mediated acetylcholine release and contraction in sheep isolated trachea. Henry, P.J., Shen, A., Mitchelson, F., Goldie, R.G. Br. J. Pharmacol. (1996) [Pubmed]
  17. Chronic intrauterine pulmonary hypertension alters endothelin receptor activity in the ovine fetal lung. Ivy, D.D., Ziegler, J.W., Dubus, M.F., Fox, J.J., Kinsella, J.P., Abman, S.H. Pediatr. Res. (1996) [Pubmed]
  18. The role of endothelin and endothelin receptor subtypes in regulation of fetal pulmonary vascular tone. Wong, J., Fineman, J.R., Heymann, M.A. Pediatr. Res. (1994) [Pubmed]
  19. Identification of conventional and novel endothelin receptors in sheep choroid plexus cells. Angelova, K., Fralish, G.B., Puett, D., Narayan, P. Mol. Cell. Biochem. (1996) [Pubmed]
  20. Endothelin-receptor blockade does not alter closure of the ductus arteriosus. Fineman, J.R., Takahashi, Y., Roman, C., Clyman, R.I. Am. J. Physiol. (1998) [Pubmed]
  21. Increased lung preproET-1 and decreased ETB-receptor gene expression in fetal pulmonary hypertension. Ivy, D.D., Le Cras, T.D., Horan, M.P., Abman, S.H. Am. J. Physiol. (1998) [Pubmed]
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