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G‐protein Coupled Receptor 30 (GPR30) in the Human Endothelium: New Roles for a Novel Estrogen Receptor
Author(s) -
Chakrabarti Subhadeep,
Davidge Sandra T
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1129.4
Subject(s) - gper , umbilical vein , microbiology and biotechnology , estrogen receptor , receptor , endothelium , agonist , chemistry , tumor necrosis factor alpha , biology , endocrinology , medicine , biochemistry , in vitro , cancer , breast cancer
Estrogen is a modulator of endothelial function. Traditionally the effects of estrogen were believed to be mediated through its classical receptors alone. There is increasing evidence of a novel G‐protein coupled receptor GPR30 in mediating some estrogenic actions. While there is evidence of vascular actions of GPR30, this protein has not been identified to date in the human endothelium and its endothelium‐specific roles are poorly understood. We used human umbilical vein endothelial cells (HUVECs) as a model system. A specific pharmacological agonist (G‐1) and an antagonist (G‐15) were used to characterize roles of GPR30. Inflammatory changes were induced by stimulation with the pro‐inflammatory cytokine tumor necrosis factor (TNF). NF‐kappaB activation was determined by degradation of inhibitor kappaB and nuclear translocation of p65. We detected GPR30 protein in HUVECs by both western blotting and immunofluorescence. GPR30 activation by G‐1 increased F‐actin and stress fibre formation in HUVECs which were prevented by G‐15 administration. G‐1 treatment also inhibited TNF‐mediated adhesion molecule expression in these cells, without altering NF‐kappaB activity. Our results suggest that endothelial GPR30 is a novel mediator of actin polymerization and anti‐inflammatory effects downstream of NF‐kappaB. This work was supported by CIHR.