G1 INDUCES ENDOTHELIUM-DEPENDENT VASORELAXATION THROUGH ACTIVATION OF EPIDERMAL GROWTH FACTOR RECEPTOR
Eun Jin Jang, Jeffrey B. Arterburn and In Kyeom Kim
Department of Pharmacology, Kyungpook National University School of Medicine, 101 Dongin-2-Ga, Daegu 700-422 Republic of Korea
Abstract:
Objectives: The G-protein-coupled-receptor 30 (GPR30) agonist G1 induces endothelium-dependent relaxation. We tested the hypothesis that G1 induces endothelium-dependent vasorelaxation through activation of epidermal growth factor (EGF) receptor.
Methods: Rat aortic rings were mounted in organ baths, and subjected to relaxation upon contraction.
Key findings: G1 induced endothelium-dependent vasorelaxation, which was attenuated by pretreatment with either L-Nω-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, or G15, a GPR30 antagonist. Neither a general estrogen receptor antagonist ICI 182,780 nor a selective estrogen receptor-α antagonist methyl-piperidino-pyrazole dihydrochloride (MPP) affected G1-induced vasorelaxation. However, pretreatment with EGF receptor blockers AG1478 or DAPH attenuated G1-induced vasorelaxation. In addition, pretreatment with Akt Inhibitor VIII, but not with a PI3K inhibitor LY294002, attenuated vascular relaxation induced by cumulative addition of G1.
Conclusions: G1 induces endothelium-dependent vasorelaxation through activation of EGF receptor and Akt pathway in rat aorta.
Keywords: G1, GPR30, EGF receptor, PI3K/Akt kinase and endothelium-dependent vasorelaxation.
ABBREVIATION: