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The mechanism of activation of G‐protein coupled estrogen receptor induced coronary artery smooth muscle relaxation
Author(s) -
Yu Xuan,
Li Fen,
Sellers Minga,
Stallone John,
White Richard,
Prossnitz Eric,
Han Guichun
Publication year - 2011
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.25.1_supplement.1009.5
Subject(s) - gper , chemistry , vascular smooth muscle , estrogen receptor , medicine , endocrinology , patch clamp , potassium channel , estrogen , coronary arteries , agonist , artery , receptor , smooth muscle , cancer , breast cancer
The G protein‐coupled estrogen receptor1 (GPER) may contribute to the non‐genomic, beneficial vascular effects of estrogen; however, the mechanism of GPER action in coronary arteries is unclear. Our objective was to determine how GPER influences coronary artery reactivity. In vitro isometric force recordings were performed on endothelium‐denuded porcine coronary arteries, and were augmented with single‐cell patch‐clamp experiments. RT‐PCR and immunoblot confirmed expression of GPER mRNA and protein, respectively, in smooth muscle from either porcine or human coronary arteries. G1 (selective GPER agonist) relaxed endothelium‐denuded porcine coronary arteries, suggesting a direct effect coronary artery smooth muscle (CASM). This response was inhibited by G15 (GPER selective antagonist), or by inhibiting large‐conductance calcium‐activated potassium (BK Ca ) channels with iberiotoxin, but inhibition of NO signaling had no effect. Interestingly, ICI182,780 (ERα/ERβ antagonist, but a GPER agonist) also relaxed coronary arteries. Lastly, whole‐cell and cell‐attached patch‐clamp studies demonstrated that G1 stimulates BK Ca channel activity in CASM cells. In summary, GPER activation relaxes CASM by increasing potassium efflux via BK Ca channels. This novel action of estrogen‐like compounds may help clarify some of the controversy surrounding the vascular effects of estrogens.