title: G-protein coupled estrogen receptor-mediated non-genomic facilitatory effect of estrogen on cooling-induced reduction of skin blood flow in mice.
abstract: An enhanced vasoconstrictor activity of cutaneous arteries participates in the reduction of skin blood flow induced by cooling stimulation. Raynaud's phenomenon, which is characterized by intense cooling-induced constriction of cutaneous arteries, is more common in women during the period from menarche to menopause. We thus investigated the effect of 17β-estradiol (E2) on cooling-induced reduction of plantar skin blood flow (PSBF) in mouse in vivo. Ovariectomized female ddY mice, anaesthetized with pentobarbital, were treated with tetrodotoxin for eliminating the sympathetic nerve tone and artificially ventilated. The PSBF was measured by laser Doppler flowmetry. Cooling air temperature around the foot from 25 to 20, 15, or 10°C decreased the PSBF in a temperature-dependent manner, which was suppressed by the specific α2C-adrenoceptor antagonist MK-912. When E2 was intravenously administered as a bolus followed by a constant infusion for 10min just before the cooling stimulation, the cooling-induced reduction of PSBF was facilitated by E2 in a dose-dependent manner. The facilitatory effect of E2 was not induced after the treatment with MK-912. Similar facilitatory effect was induced by an intravenous application of G-1, an agonist of G protein-coupled estrogen receptor (GPER, also termed GPR30). Moreover, the facilitatory effect of E2 was abolished by the GPER antagonist G15. These results suggest that acute administration of E2 leads to the facilitation of cooling-induced, α2C-adrenoceptor-mediated reduction of skin blood flow via the activation of the non-genomic estrogen receptor GPER.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Serizawa
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Saito
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan. Electronic address: ishikat@u-shizuoka-ken.ac.jp.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D051379:Mice; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects*; D012867:Skin / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol
keywords: Cold-induced vasoconstriction; Estrogen; G protein-coupled estrogen receptor; Laser Doppler flowmetry; Mouse; Skin blood flow