GPR30/GPER is a novel G protein-coupled estrogen receptor. Using a rabbit polyclonal antiserum against the human GPR30 C-terminus, we identified GPR30 immunoreactivity in the cytoplasm of human aortic endothelial cells (HAEC). Administration of G-1, a selective GPR30 agonist or 17b-estradiol (E2) to HAEC produced a fast and sustained increase in intracellular Ca2+ concentrations [Ca2+]i. G-1 (0.01 μM, 0.1 μM and 1 μM) increased [Ca2+]i by 93 + 3.2, 176 + 4.2, and 558 + 6.9 nM, respectively. E-2 (15 μM) increased [Ca2+]i by 127 + 2.1 nM. Activation of GPR30 caused NO production in HAEC and NO-dependent aortic ring relaxation. G-1 (1 μM) or E2 (15 μM) increased ΔDAF (F/F0) fluorescence by 0.09 + 0.009 and 0.07 + 0.009, respectively, while acetylcholine (15 μM) increased ΔDAF by 0.31 + 0.01. Administration of G-1 (0.01 μM, 0.1 μM and 1 μM) produced HAEC hyperpolarization with an amplitude of 4 + 1.9 mV, 18 + 3.6 mV, and 28 + 3.8 mV, respectively. E2 (15 μM) hyperpolarized HAEC by 16 + 2.6 mV. Intravenous administration of G-1 (41.2 ng/kg to 41.2 μg/kg) to urethane-anesthetized Sprague Dawley rats produced a dose-dependent decrease (by 2.6 + 1.6 % to 14.7 + 1.1%) in mean arterial pressure. Taken together, our results indicate that GPR30 is involved in the vascular response to estrogen.
University College Dublin (2009) Proc Physiol Soc 15, PC154
Poster Communications: Vascular responses mediated by GPR30/GPER
E. Brailoiu1, A. A. Tica1, C. G. Brailoiu1, J. B. Arterburn2, M. Barton3, E. R. Prossnitz4, T. I. Oprea5, N. J. Dun1
1. Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. 2. Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico, USA. 3. Departement für Innere Medizin, Universitätsspital Zürich, Zürich, Switzerland. 4. Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA. 5. Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
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