| dc.description.abstract | GPER is a membrane-bound estrogen receptor, distinct from ERα or ERβ, and exerts genomic and non-genomic effects. GPER’s effect on the cardiovascular system has been controversial; evidence indicates it relaxes arteries, whereas other findings suggest it contracts arteries. Our objective is to better understand the dual nature of GPER. Previously, our work demonstrated that G-1 stimulates cAMP production. I hypothesize GPER mediates relaxation response through cAMP and constriction via ERK1/2. Isometric tension studies were used to measure GPER-mediated coronary tone response in porcine coronary arteries. Western blots were applied to detect pERK1/2 in primary cell culture of smooth muscle cells. The identity of smooth muscle cells was validated by immunohistochemistry techniques using α actin as a marker. G-1 inhibited phosphorylation; however, under adenylyl cyclase inhibition by SQ22536, G-1 stimulated phosphorylation of ERK1/2. The effect of G-1 was blocked by G36, a GPER inhibitor. A time course of E2 (100 nM) demonstrated E2 acutely stimulated phosphorylation of ERK1/2. Tension studies demonstrated that G-1 caused concentration-dependent relaxation of PGF2α (1 μM) precontracted, endothelium denuded, coronary arteries. PD98059, a MEK inhibitor that blocks the phosphorylation of ERK1/2, led to further relaxation than G-1 alone. I conclude that phosphorylation of ERK1/2 lessens the coronary artery relaxation caused by GPER. | en |
