Chronic activation of the G protein-coupled receptor 30 with agonist G-1 attenuates heart failure

PLoS One. 2012;7(10):e48185. doi: 10.1371/journal.pone.0048185. Epub 2012 Oct 26.


G protein-coupled receptor (GPR) 30 is a novel estrogen receptor. Recent studies suggest that activation of the GPR30 confers rapid cardioprotection in isolated rat heart. It is unknown whether chronic activation of GPR30 is beneficial or not for heart failure. In this study we investigated the cardiac effect of sustained activation or inhibition of GPR30. Female Sprague-Dawley rats were divided into 7 groups #2Q1: sham surgery (Sham), bilateral ovariectomy (OVX), OVX+estrogen (E(2)), OVX+isoproterenol (ISO), OVX+ISO+G-1, OVX+ISO+E(2)+G15, OVX+ISO+E(2). ISO (85 mg/kg×17 day, sc) was given to make the heart failure models. G-1(120 µg/kg·d×14 day) was used to activate GPR30 and G15 (190 µg/kg·d×14 day) was used to inhibit GPR30. Concentration of brain natriuretic peptide in serum, masson staining in isolated heart, contractile function and the expression of β(1) and β(2)- adrenergic receptor (AR) of ventricular myocytes were also determined. Our data showed that ISO treatment led to heart failure in OVX rats. G-1 or E(2) treatment decreased concentration of brain natriuretic peptide, reduced cardiac fibrosis, and enhanced contraction of the heart. Combined treatment with β(1) (CGP20712A) and β(2)-AR (ICI118551) antagonist abolished the improvement of myocardial function induced by G-1. We also found that chronic treatment with G-1 normalized the expression of β(1)-AR and increased the expression of β(2)-AR. Our results indicate that chronic activation of the GPR30 with its agonist G-1 attenuates heart failure by normalizing the expression of β(1)-AR and increasing the expression of β(2)-AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclopentanes / therapeutic use*
  • Estrogens / therapeutic use
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism*
  • Isoproterenol / therapeutic use
  • Natriuretic Peptide, Brain / metabolism
  • Ovariectomy
  • Quinolines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism*


  • 1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone
  • Cyclopentanes
  • Estrogens
  • Gper1 protein, rat
  • Quinolines
  • Receptors, G-Protein-Coupled
  • Natriuretic Peptide, Brain
  • Isoproterenol

Grant support

This work was supported by the President Support Funding of Xuzhou Medical College (grant number 09KJZ31) and the Social Development Program of Xuzhou (grant number XM08C063). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.