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Rapid estrogen signaling via GPR30 in coronary artery smooth muscle
Author(s) -
Han Guichun,
Barman Scott A.,
White Richard E.
Publication year - 2009
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.23.1_supplement.968.5
Subject(s) - gper , estrogen receptor , medicine , vascular smooth muscle , coronary arteries , endocrinology , estrogen , potassium channel , electrical impedance myography , artery , chemistry , cardiology , vasodilation , smooth muscle , cancer , breast cancer
There is no clear understanding of how coronary artery function is regulated by estrogen (E2), which can either relax or contract arteries via rapid, non‐genomic mechanisms involving classic estrogen receptors (ER). Our objective was to investigate non‐genomic E2 signaling mechanisms in coronary artery smooth muscle. In addition to ERα and ERβ, E2 may also stimulate a G protein‐coupled estrogen receptor, GPR30, in non‐vascular tissue; however, a potential role for GPR30 in coronary arteries is unknown. We found that G1, a selective GPR30 agonist, produces a concentration‐dependent relaxation of endothelium‐denuded porcine coronary arteries in vitro (EC50, 26.5 nM). Further, this response was inhibited by 1mM tetraethylammonium, an inhibitor of large‐conductance calcium‐activated potassium (BKCa) channels. Interestingly, ICI182,780, a non‐selective ER antagonist which can activate GPR30, also induced a concentration‐dependent relaxation of endothelium‐denuded coronary arteries (EC50, 137 nM) contracted with PGF2α, but was far less effective in relaxing arteries contracted with 30mM KCl. Immunoblot studies detected expression of GPR30 protein in smooth muscle from either porcine or human coronary arteries. These studies suggest a novel estrogen signaling mechanism in coronary arteries: stimulation of GPR30, leading to potassium efflux and membrane hyperpolarization. (Supported by HL73890)