Search for agonists of new plasma membrane estrogen receptors and their anti-stress effects

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: TAKAHASHI Kojiro 産業医科大学, 医学部, 非常勤講師 (70389477)
• Co-Investigator(Kenkyū-buntansha): YANAGIHARA Nobuyuki 産業医科大学, 医学部, 教授 (80140896)
• Project Period (FY): 2011 – 2013
• Keywords: カテコールアミン生合成 / カテコールアミン分泌 / 抗ストレス効果 / 細胞膜エストロゲン受容体 / 受容体作動薬 / 植物性エストロゲン / 植物フラボノイド / ノルアドレナリントランスポーター

Research Abstract

The agonists of plasma membrane estrogen receptors were investigated. Daidzein and genistein, soy isoflavones, and resveratrol, a grape polyphenol, inhibited the specific binding of [3H]17beta-estradiol to plasma membranes isolated from bovine adrenal medulla. These phytoestrogens and a plant flavonoid, nobiletin, inhibited catecholamine synthesis and secretion induced by acetylcholine in cultured bovine adrenal medullary cells. Resveratrol also affected the function of noradrenaline transporter in SK-N-SH cells (human neuroblastoma cell line). These results suggest that phytoestrogens and some plant flavonoids have protective effects against stresses.

Research Products

• [Journal Article] Inverse correlation between the standard deviation of R-R intervals in the supine position and the simplified menopausal index in women with climacteric symptoms (2014)
  • Author(s): Yanagihara N., Seki M., Nakano M., Hachisuga T., Goto Y
  • Journal Title: Menopause Volume: 21(in press)
  • Peer Reviewed
• [Journal Article] New Insights into the Pharmacological Potential of Plant Flavonoids in the Catecholamine System (2014)
  • Author(s): Yanagihara N., Zhang H., Toyohira Y., Takahashi K., Ueno S., Tsutsui M., Takahashi K
  • Journal Title: J Pharmacol Sci Volume: 124 Pages: 123-128
  • DOI: 10.1254/jphs.13R17CP
  • Peer Reviewed
• [Journal Article] Effects of food deprivation on the hypothalamic feeding-regulating peptides gene expression in serotonin depleted rats (2014)
  • Author(s): Yoshimura M., Hagimoto M., Matsuura T., Ohkubo J., Ohno M., Maruyama T., Ishikura T., Hashimoto H., Kakuma T., Yoshimatsu H., Terawaki K., Uezono Y., Toyohira Y., Yanagihara N., Ueta Y
  • Journal Title: J Physiol Sci Volume: 64 Pages: 97-104
  • DOI: 10.1007/s12576-013-0296-1
  • Peer Reviewed
• [Journal Article] Effects of selective estrogen receptor modulators on plasma membrane estrogen receptors and catecholamine synthesis and secretion in cultured bovine adrenal medullary cells (2014)
  • Author(s): Inagaki H., Toyohira Y., Takahashi K., Ueno S., Obara G, Kawagoe T., Tsutsui M., Hachisuga T., Yanagihara N
  • Journal Title: J Pharmacol Sci Volume: 124 Pages: 66-75
  • DOI: 10.1254/jphs.13155FP
  • Peer Reviewed
• [Journal Article] Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine synthesis through Ser^<19> and Ser^<40> phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells (2014)
  • Author(s): Zhang H., Yanagihara N., Toyohira Y., Takahashi K., Inagaki H., Li X., Tsutsui M., Takahashi K
  • Journal Title: Naunyn-Schmiedeberg's Arch of Pharmacol Volume: 387 Pages: 15-22
  • DOI: 10.1007/s00210-013-0916-6
  • Peer Reviewed
• [Journal Article] Antagonism of cortex periplocae extract-induced catecholamines secretion by Panax notoginseng saponins in cultured bovine adrenal medullary cell by drug combinations (2013)
  • Author(s): Guo H., Mao H., Zhang H., Fan G., Li G., Zhou K., Zhu Y., Yanagihara N., Gao X
  • Journal Title: J Ethenopharmacol Volume: 147 Pages: 447-455
  • DOI: 10.1016/j.jep.2013.03.036
  • Peer Reviewed
• [Journal Article] Nitric oxide synthase and heart failure-Lesson from genetically manipulated mice (2013)
  • Author(s): Shibata K., Shimokawa H., Yanagihara N., Otsuji Y., Tsutsui M
  • Journal Title: J UOEH Volume: 35 Pages: 147-158
  • Peer Reviewed
• [Journal Article] Long-term treatment with San'o-Shashin-To, a Kampo Medicine, markedly ameliorates cardiac ischemia-reperfusion injury in ovariectomized rats via the redox-dependent mechanism (2013)
  • Author(s): Sakanashi M., Matsuzaki T., Noguchi K., Nakasone J., Sakanashi M., Uchida T., Tanimoto A., Yanagihara N., Sakanashi M., Ohya Y., Masuzaki H., Ishiuchi S., Sugahara K., Tsutsui M
  • Journal Title: Circulation J Volume: 77 Pages: 1827-1837
  • DOI: 10.1253/circj.CJ-12-1434
  • Peer Reviewed
• [Journal Article] Pentazocine inhibits norepinephrine transporter function by reducing its surface expression in bovine adrenal medullary cells (2013)
  • Author(s): Obara G., Toyohira Y., Inagaki H., Takahashi K., Horishita T., Ueno S., Tsutsui M., Yanagihara N
  • Journal Title: J Pharmacol Sci Volume: 121 Pages: 138-147
  • DOI: 10.1254/jphs.12164FP
  • Peer Reviewed
• [Journal Article] Inhibition by pregnenolone sulphate, a metabolite of the neurosteroid pregnenolone, of voltage-gated sodium channels expressed in Xenopus oocytes (2012)
  • Author(s): Horishita T., Ueno S., Yanagihara N., Sudo Y., Uezono Y., Okura D., Sata T
  • Journal Title: J Pharamcol Sci Volume: 120 Pages: 54-58
  • DOI: 10.1254/jphs.12106SC
  • Peer Reviewed
• [Journal Article] Stimulation of norepineph- rine transporter function by fasudil, a Rho kinase inhibitor, in cultured bovine adrenal medullary cells (2012)
  • Author(s): Satoh N., ToyohiraY., Itoh H., Zhang H., Ueno S., Tsutsui M., Takahashi K., Yanagihara N
  • Journal Title: Naunyn-Schmiedeberg's Archives of Pharmacol Volume: 385 Pages: 921-931
  • DOI: 10.1007/s00210-012-0773-8
  • Peer Reviewed
• [Journal Article] 習慣飲酒の更年期障害症候群患者に対する加味逍遥散の有用性 (2012)
  • Author(s): 石明寛、広渡加奈子、椎葉美代子、蜂須賀徹、土岐尚之、柳原延章、石政維、上田恵、吉武英憲
  • Journal Title: Science of Kampo Medicine Volume: 36 Pages: 55-59
  • Peer Reviewed
• [Journal Article] Influence of work shift on glutamic acid and gamma-aminobutyric acid (GABA): Evaluation with proton magnetic resonance spectroscopy at 3T (2011)
  • Author(s): Kakeda S., Korogi Y., Moriya J., Ohnari N., Sato T., Ueno S., Yanagihara N., Harada M., Matsuda T
  • Journal Title: Psychiatric Research : Neuroimaging Volume: 192 Pages: 55-59
  • DOI: 10.1016/j-pscychresns.2010.10.011
  • Peer Reviewed
• [Journal Article] Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle (2011)
  • Author(s): Kubota T., Kubota N., Kumagai H., Yamaguchi S., Kozono H., Takahashi T., Inoue M., Itoh S., Takamoto I., Sasako T., Kumagai K., Kawai T., Hashimoto S., Kobayashi T. Sato M., Tokuyama K., Nishimura S., Tsunoda M., Ide T. Murakami K., Yamazaki T., Ezaki O., Kawamura K., Masuda H., Moroi M., Sugi K., Oike Y., Shimokawa H., Yanagihara N., Tsutsui M., Terauchi Y., Tobe K., Nagai R., Kamata K., Inoue K., Kodama T., Ueki K., Kadowaki T
  • Journal Title: Cell Metabolism Volume: 13 Pages: 294-307
  • DOI: 10.1016/j.cmet.2011.01.018
  • Peer Reviewed
• [Journal Article] Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice : Involvement of bone marrow-derived cells (2011)
  • Author(s): Furuno Y., Morishita T., Toyohira Y., Yamada S., Ueno S., Morisada N., Sugita K., Noguchi K., Sakanashi M., Miyata H., Tanimoto A., Sasaguri Y., Shimokawa H., Otsuji Y., Yanagihara N., Tamura M., Tsuttsui M
  • Journal Title: Nitric Oxide Volume: 25 Pages: 350-359
  • DOI: 10.1016/j.niox.2011.06.007
  • Peer Reviewed
• [Journal Article] Dendritic cell-derived dopamine induces IL-6-dependent Th17 polarization in rheumatoid arthritis (2011)
  • Author(s): Nakano K., Matsushita S., Yamaoka K., Saito K., Sasaguri Y., Yanagihara N., Tanaka S., Katsuki I, Tanaka Y
  • Journal Title: J Immunology Volume: 186(6) Pages: 3745-3752
  • DOI: 10.4049/jimmunol.1002475
  • Peer Reviewed
• [Journal Article] Stimulation of IFN-gamma production by garlic lectin in mouse spleen cells : Involvement of IL-12 via activation of p38 MAPK and ERK in macrophages (2011)
  • Author(s): Dong Q., Sugiura T., Toyohira Y., Yoshida Y., Yanagihara N., Karasaki Y
  • Journal Title: Phytomedicine Volume: 18 Pages: 309-316
  • DOI: 10.1016/j-phymed.2010.06.008
  • Peer Reviewed
• [Journal Article] Reduced spinal microglial activation and neuropathic pain after nerve injury in mice lacking three nitric oxide synthases (2011)
  • Author(s): Kuboyama K., Tsuda M., Tsutsui M., Toyohira Y., Saitoh-Tozaki H., Shimokawa H., Yanagihara N., Inoue K
  • Journal Title: Mol Pain Volume: 7 Pages: 50
  • URL: http://www.molecularpain.com/content/7/1/50
• [Presentation] ノルアドレナリントランスポーターの赤ワインポリフェノールによる機能調節 (2014)
  • Author(s): 豊平由美子、小原剛、稲垣博英、高橋圭太、李暁佳、高橋浩二郎、柳原延章
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター、仙台
  • Year and Date: 2014-03-21
• [Presentation] 交感神経ー副腎髄質機能における免疫系及び植物性フラボノイドによる修飾 (2014)
  • Author(s): 柳原延章、豊平由美子、高橋圭太、稲垣博英、李暁佳、上野晋、筒井正人、高橋浩二郎
  • Organizer: 第87回日本薬理学会年会シンポジウム
  • Place of Presentation: 仙台国際センター、仙台
  • Year and Date: 2014-03-20
• [Presentation] 更年期障害患者における自律神経バランス変動の評価 (2014)
  • Author(s): 柳原延章、石明寛、中野正博、蜂須賀徹、後藤幸生
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター、仙台
  • Year and Date: 2014-03-20
• [Presentation] 選択的エストロゲン受容体調整薬タモキシフェン、ラロキシフェンのカテコールアミン生合成、分泌に及ぼす影響 (2014)
  • Author(s): 稲垣博英、豊平由美子、高橋圭太、上野晋、小原剛、筒井正人、高橋浩二郎、李暁佳、蜂須賀徹、柳原延章
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター、仙台
  • Year and Date: 2014-03-20
• [Presentation] The effects of nicergoline, an ameliorator of cerebral circulation and metabolism, on the monoamine transporter (2013)
  • Author(s): Itoh H., Toyohira Y., Matsushima Y., Ueno S., Saeki S., Yanagihara N., Hachisuka K
  • Organizer: 43th Society for Neuroscience Annual Meeting
  • Place of Presentation: San Diego Convention Center, San Diego
  • Year and Date: 20131109-13
• [Presentation] A novel vasculoprotective role of nitric oxide synthases in bone marrow-derived vascular progenitor cells (2013)
  • Author(s): Tsutsui M, Furuno Y, Morishita T, Yanagihara N, Tamura M, Shimokawa H, Otsuji Y
  • Organizer: American Heart Association, Scientific Sessions
  • Place of Presentation: Dallas Convention Center, Dallas, Texas USA
  • Year and Date: 2013-11-18
• [Presentation] Dual effects of nobiletin, a citrus polymethoxy flavones, on catecholamine signaling in cultured bovine adrenal medullary cells (2013)
  • Author(s): Zhang H. , Yanagihara N. , Toyohira Y., Takahashi K., Takahashi K
  • Organizer: 37th Congress of the International Union of Physiological Sciences
  • Place of Presentation: International Convention Center, Birmingham, UK
  • Year and Date: 2013-07-24
• [Presentation] ノルアドレナリントランスポーター機能に対するレスベラトロールの作用 (2013)
  • Author(s): 豊平由美子、小原剛、稲垣博英、高橋圭太、高橋浩二郎、柳原延章
  • Organizer: 第13回日本NO学会
  • Place of Presentation: 沖縄県医師会館、那覇
  • Year and Date: 2013-06-28
• [Presentation] (2013)
  • Author(s): 稲垣博英、豊平由美子、高橋圭太、高橋浩二郎、小原剛、上野晋、筒井正人、蜂須賀徹、柳原延章
  • Organizer: 第65回日本産婦人科学学術講演
  • Place of Presentation: ロイトン札幌、札幌市
  • Year and Date: 2013-05-11
• [Presentation] ウシ副腎髄質細胞の機能における選択的エストロゲン調整薬の影響について (2013)
  • Author(s): 稲垣博英・豊平由美子・小原剛・蜂須賀徹・柳原延章
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2013-03-23
• [Presentation] Rhoキナーゼ阻害剤ファスジルによるノルエピネフリントランスポーター機能促進 (2013)
  • Author(s): 佐藤教昭、豊平由美子、高橋圭太、上野晋、筒井正人、柳原延章
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場、福岡
  • Year and Date: 2013-03-23
• [Presentation] Significance of the Nitric Oxide Synthase System in the Pathogenesis of the Cardiovascular System (2013)
  • Author(s): 筒井正人、下川宏明、尾辻豊、柳原延章
  • Organizer: 第86回日本薬理学会年会シンポジウム
  • Place of Presentation: 福岡国際会議場、福岡
  • Year and Date: 2013-03-22
• [Presentation] レスベラトロールはノルアドレナリントランスポーター機能を2相性に調節する (2013)
  • Author(s): 豊平由美子、小原剛、稲垣博英、高橋圭太、高橋浩二郎、柳原延章
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場、福岡
  • Year and Date: 2013-03-22
• [Presentation] ペンタゾシンのモノアミントランスポータ活性に及ぼす影響 (2013)
  • Author(s): 小原剛, 豊平由美子・稲垣博英・高橋浩二郎・上野晋・佐多竹良・柳原延章
  • Place of Presentation: 福岡国際会議場、福岡
  • Year and Date: 2013-03-21
• [Presentation] Development of an experimentally useful animal model of spontaneous myocardial infarction (2013)
  • Author(s): Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Ohya Y, Yanagihara N, Shimokawa H, Tamura M, Otsuji Y, Tsutsui M
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Pacifico Yokohama, Yokohama
  • Year and Date: 2013-03-15
• [Presentation] The effects of nicergoline, an ameliorator of cerebral circulation and metabolism, on the monoamine Transporter (2012)
  • Author(s): Itoh H., Toyohira Y., Matsushima Y., Ueno S., Saeki S., Yanagihara N., Hachisuka K
  • Organizer: 8th WORLD STROKE CONGRESS
  • Place of Presentation: Ulysses Guimarães Convention Center, Brasilia, Brazil
  • Year and Date: 2012-10-12
• [Presentation] Plant flavonoids affecting adrenal medullary catecholamine biosynthesis and release (2012)
  • Author(s): Yanagihara N., Toyohira Y., Ueno S., Tsutsui M., Zhang H
  • Organizer: 10^<th> International Catecholamine symposium
  • Place of Presentation: Asiloma Conference Granunds, Asiloma, CA, USA
  • Year and Date: 2012-09-11
• [Presentation] Novel vasculoprotective role of nitric oxide synthase (NOS) in Mice : Involvement of Bone-Marrow- Derived Vascular Progenitor Cells (2012)
  • Author(s): Furuno Y, Tsutsui M, Morishita T, Shimokawa H, Otsuji Y, Yanagihara N, Kabashima N, Serino R., Kanegae K, Miyamoto T, Nakamata J, Ishimatsu N, Tamura M
  • Organizer: The 49th European Renal Association- European Dialysis and Transplant Association Congress
  • Place of Presentation: Palais des Congres, Paris, France
  • Year and Date: 2012-05-24
• [Presentation] Novel vasculoprotective role of nitric oxide synthases in bone-marrow-derived vascular progenitor cells (2012)
  • Author(s): Tsutsui M, Furuno Y, Morishita T, Yanagihara N, Tamura M, Shimokawa H, Otsuji Y
  • Organizer: The 76th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Fukuoka Kokusai Center, Fukuoka, Japan
  • Year and Date: 2012-03-18
• [Presentation] 赤ワイン含有のフラボノール類のカテコールアミン分泌に及ぼす影響 (2012)
  • Author(s): 坂巻路可・豊平由美子・外山健二・柳原延章
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 京都国際会議場、京都
  • Year and Date: 2012-03-16
• [Presentation] 選択的エストロゲン受容体調整薬の副腎髄質細胞のカテコールアミン分泌に与える影響について (2012)
  • Author(s): 稲垣博英・豊平由美子・小原剛・蜂須賀徹・柳原延章
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 京都国際会議場、京都
  • Year and Date: 2012-03-16
• [Presentation] 植物フラボノイドのカテコールアミンシグナリングへの作用とその創薬的基盤研究 (2012)
  • Author(s): 柳原延章・豊平由美子・上野晋・筒井正人・張唅
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都国際会議場、京都 (シンポジウム)
  • Year and Date: 2012-03-15
• [Presentation] 赤ワインポリフェノールのレスベラトロールがノルアドレナリントランスポーター機能に及ぼす影響 (2012)
  • Author(s): 豊平由美子・小原剛・稲垣博英・坂巻路可・高橋浩二郎・柳原延章
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都国際会議場、京都
  • Year and Date: 2012-03-14
• [Presentation] Ca^<2+>-dependent effects of nobiletin, a citrus flavonoid, on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells (2011)
  • Author(s): Yanagihara N., Zhang H., Toyohira Y., Ueno S., Tsutsui M., Takahashi K
  • Organizer: 7^<th> International Forum on the Development of Traditional Chinese Medicine
  • Place of Presentation: Tianjin, China
  • Year and Date: 2011-09-21
• [Presentation] Complete Disruption of All Nitric Oxide Synthase Genes Causes Markedly Accelerated Renal Lesion Formation in Mice in vivo (2011)
  • Author(s): Morisada N, Iijima K, Matsuo M, Shimokawa H, Yanagihara N, Tsutsui M
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Pacifico Yokohama, Yokohama, Japan
  • Year and Date: 2011-08-03
• [Presentation] Accelerated Vascular Lesion Formation in Mice Lacking All Nitric Oxide Synthases : Contribution of Bone Marrow Cells (2011)
  • Author(s): Furuno Y, Morishita T, Yanagihara N, Shimokawa H, Otsuji Y, Tamura M, Tsutsui M
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Pacifico Yokohama, Yokohama, Japan
  • Year and Date: 2011-08-03
• [Presentation] Effects of flavonoids on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells (2011)
  • Author(s): Yanagihara N., Zhang H., Toyohira Y., Ueno S., Tsutsui M., Takahashi K
  • Organizer: The 8th IBRO World Congress of Neuroscience
  • Place of Presentation: Florence, Italy
  • Year and Date: 2011-07-20
• [Book] Insight into the pharmacological effects of soy isoflavones on catecholamine system. In Soybean and Health (edited by El-Shemy H.)
  • Author(s): Yanagihara N. Toyohira Y., Liu M., Ueno S., Tsutsui M., Zhang H
  • Total Pages: 167-180
  • Publisher: INTECH, Croatia