Basic study on a new membrane estrogen receptor and search for its selective agonist

• Project/Area Number: 20611020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: YANAGIHARA Nobuyuki University of Occupational and Environmental Health, Japan, 医学部, 教授 (80140896)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞膜エストロゲン受容体 / 植物性エストロゲン / カテコールアミン / 中国薬草 / ニコチン / ノビレチン / ノルエピネフリントランスポーター / 副腎髄質細胞 / エストロゲン受容体 / カテコールアミン分泌 / 更年期障害治療薬 / カテコールアミン生合成 / 細胞膜 / 女性ホルモン代用薬

Research Abstract

In the present study, we examined the effects of phytoestrogens on catecholamine (CA) dynamics in cultured bovine adrenal medullary cells. Genistein, a soy phytoestrogen, and nicotine, a major component of tobacco, stimulated the function of norepinephrine transporter (NET). Nobiletin, a component of peel of citrus fruits, suppressed CA synthesis and secretion induced by acetylcholine. The present findings suggest that genistein, nicotine, and nobiletin have a pharmacological potential on cardiovascular protective effects.

Research Products

• [Journal Article] Impaired Insulin Signaling in Endothelial C ells 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 (in press)
  • Peer Reviewed
• [Journal Article] Stimulatory effects of the soy phytoestrogen genistein onoradrenaline transporter and serotonin transporter activity. (2010)
  • Author(s): Toyohira Y., Ueno S., Tsutsui M., Itoh H., Sakai N., Saito N., Takahashi K., Yanagihara N.
  • Journal Title: Mol Nutr Food Res. 54(4) Pages: 516-524
  • Peer Reviewed
• [Journal Article] Upregulation of norepinephrine transporter function by prolonged exposure to nicotine in cultured bovine adrenal medullary cells (2010)
  • Author(s): Itoh H., Toyohira Y., Ueno S., Saeki S., Zhang H., Furuno Y., Takahashi K., Tsutsui M., Hachisuka K., Yanagihara N.
  • Journal Title: Naunyn-Schmiedeberg's Arch Pharmacol. 382 Pages: 235-243
  • Peer Reviewed
• [Journal Article] Dual effects nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells (2010)
  • Author(s): Zhang H., Toyohira Y., Ueno S., Shinohara Y., Itoh H., Furuno Y.,Yamakuni T., Tsutsui M., Takahashi K., Yanagihara N.
  • Journal Title: J. Neurochem. 114(4) Pages: 1030-1038
  • Peer Reviewed
• [Journal Article] Stimulatory effects of the soy phytoestrogen genistein on noradrenaline transporter and serotonin transporter activity (2010)
  • Author(s): Yumiko Toyohira
  • Journal Title: Molecular Nutrition Food Research Volume: 54 Pages: 516-524
  • Peer Reviewed
• [Journal Article] Dual effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullarv cells (2010)
  • Author(s): Han Zhang
  • Journal Title: Journal of Neurochemistry Volume: 114 Pages: 1030-1038
  • Peer Reviewed
• [Journal Article] Upregulation of norepinephrine transporter function by prolonged exposure to nicotine in cultured bovine adrenal medullary cells (2010)
  • Author(s): Hideaki Itoh
  • Journal Title: Naunyn-Schmiedeberg's Arch of Pharmacol Volume: 382 Pages: 235-243
  • Peer Reviewed
• [Journal Article] Stimulatory Effects of the Soy Phytoestrogen Genistein on Noradrenalin Transporter and SerotoninTransporter Activity (2010)
  • Author(s): Toyohira Y., Ueno S., Tsutsui M., Itho H., Sakai N., Saito N., Takahashi K., Yanagihara N.
  • Journal Title: Molecular Nutrition and Food Research (in press)
  • Peer Reviewed
• [Journal Article] Antagonistic effects of two herbs in Zuojin Wan, a traditional Chinese medicine formula, on catecholamine secretion in bovine adrenal medullary cells (2010)
  • Author(s): Fenrong Zhao, Haoping Mao, Han Zhang, Limin Hu, Hong Wang, Yuefei Wang, Nobuyuki Yanagihara, XiumeiGao
  • Journal Title: Phytomedicine (in press)
  • Peer Reviewed
• [Journal Article] Inducible nitric oxide synthase downmodulates contact hypersensitivity by suppressing dendric cell migration and survival (2010)
  • Author(s): Sugita K., Kabashima K., Yoshiki R., Ikenouchi-Sugita A., Tsutsui M., NakamuraJ., Yanagihara N., Yoshiki Tokura
  • Journal Title: Journal Investigative Dermatology (in press)
  • Peer Reviewed
• [Journal Article] Dual effects of lipophilic extract of Salvia miltiorrhiza (Danshen) on catecholamine secretion in cultured bovine adrenal medullary cells. (2009)
  • Author(s): Mao H, Zhang H, Wang H, Wang Y, Zhao F, Hu L, Yanagihara N, Gao X
  • Journal Title: J Ethnopharmacol. 125(1) Pages: 59-67
  • Peer Reviewed
• [Journal Article] Dual effects of lipophilic extract of Salvia miltiorrhiza (Danshen) on catecholamine secretion in cultured bovine adrenal medullary cells. (2009)
  • Author(s): Mao H, Zhang H, Wang H, Wang Y, Zhao F, Hu L, Yanagihara N., Gao X.
  • Journal Title: J Ethnopharmacol 125 Pages: 59-67
  • Peer Reviewed
• [Journal Article] 一酸化窒素合成酵素システムと骨代謝 (2009)
  • Author(s): 佐羽内研、筒井正人、酒井昭典、下川宏明、柳原延章、中村利孝
  • Journal Title: Orthopaedic Surgery and Traumatology 52 Pages: 1252-1253
• [Journal Article] Opposite effects of milnacipran, a serotonin norepinephrine reuptake in hibitor, on the level of nitric oxide and brain-derived neurotrophic factor in mouse brain cortex (2009)
  • Author(s): Ikenouchi-Sugita A., Toyohira Y., Yoshimura R., Ueno S., Tsutsui M., Nakamura J., Yanagihara N
  • Journal Title: Naunyn-Schmiedeberg's Arch Pharmacol 380 Pages: 479-486
  • Peer Reviewed
• [Journal Article] Spontaneous myocardial infarction and nitric oxide synthase. (2009)
  • Author(s): Tsutsui M., Nakata S., Shimokawa H., Otsuji Y., Yanagihara N.
  • Journal Title: Trends Cardiovasc Med (Review) (in press)
  • Peer Reviewed
• [Journal Article] Insights into the pharmacological potential of estrogens and phytoestrogens on catecholamine signaling. (2008)
  • Author(s): Yanagihara N., Toyohira Y., Shinohara Y
  • Journal Title: Annals of NY Academy Sciences 1129 Pages: 96-104
  • Peer Reviewed
• [Journal Article] Simvastatin inhibits catecholamine secretion and synthesis induced by acetylcholine via blocking Na^+ and Ca^<2+> influx in bovine adrenal medullary cells. (2008)
  • Author(s): Matsuda T, Toyohira Y, Ueno S, Tsutsui M, Yanagihara N.
  • Journal Title: J Pharmacol Exp Ther 327 Pages: 130-136
  • Peer Reviewed
• [Journal Article] Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice. (2008)
  • Author(s): Takai A, Morikawa K, Tsutsui M, Murayama Y, Tekes E, Yamagishi H, Ohashi J, Yada T, Yanagihara N, Shimokawa H
  • Journal Title: J Exp Med 205 Pages: 20530-2063
  • Peer Reviewed
• [Journal Article] Spontaneous myocardial infarction in mice lacking all three nitric oxide synthase. (2008)
  • Author(s): Nakata S., Tsutsui M., Shimokawa H., Morishita T., Sabanai K., Nagasaki M., Tanimoto A., Suda O., Yatera Y., Shibata K., Tasaki H., Sasaguri Y., Nakashima Y., Otuji Y., Yanagihara N.
  • Journal Title: Circulation 117 Pages: 2211-2223
  • Peer Reviewed
• [Journal Article] 植物性エストロゲンのカテコールアミン生合成・分泌への影響 (2008)
  • Author(s): 柳原延章、豊平由美子、上野晋、筒井正人、篠原優子、劉民慧
  • Journal Title: 日本薬理学雑誌 132 Pages: 150-154
  • NAID: 10024383759
  • Peer Reviewed
• [Journal Article] 植物性エストロゲンのカテコールアミン生合成・分泌への影響 (2008)
  • Author(s): 柳原延章, 豊平由美子, 上野晋, 筒井正人, 篠原優子, 劉民慧
  • Journal Title: 日本薬理学雑誌 132 Pages: 150-154
  • NAID: 10024383759
  • Peer Reviewed
• [Journal Article] Insights into the pharmacological potential of estrogens and phytoestrogens on catecholamine signaling. (2008)
  • Author(s): Yanagihara N., Toyohira Y., Shinohara Y.
  • Journal Title: Annals of NY Academy Sciences 1129 Pages: 96-104
  • Peer Reviewed
• [Journal Article] Crucial Role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice. (2008)
  • Author(s): Takaki A., Morikawa K., Tsutsui M., Murayama Y., Tekes E., Yamagishi H., Yanagihara N., Shimokawa H.
  • Journal Title: J Exp Med. 205 Pages: 2053-2063
  • Peer Reviewed
• [Journal Article] Simvastatin inhibits catecholamine secretion and synthesis induced by acetylcholine via blocking Na^+ and Ca^<2+> influx in bovine adrenal medullary cells. (2008)
  • Author(s): Matsuda T., Toyohira Y., Ueno S., Tsutsui M., Yanagihara N.
  • Journal Title: J Pharmacol Exp Ther 327 Pages: 1-7
  • Peer Reviewed
• [Presentation] New insights into the pharmacological potential of plant flavonoids on catecholamine signaling. (2011)
  • Author(s): Yanagihara N., Zhang H., Toyohira Y., Ueno S., Tsutsui M., Takahashi K.
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-23
• [Presentation] Daual effects of nobiletin, a citrus polymethoxy flavones, on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells. (2011)
  • Author(s): Zhang H., Toyohira Y., Ueno S., Tsutsui M., Itoh H., Takahashi K., Yanagihara N.
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-22
• [Presentation] Stimulation of Noradrenaline Transporter and Serotonin Transporter Activity by Soy Phytoestrogen Genistein. (2010)
  • Author(s): Yanagihara N., Toyohira Y., Ueno S., Tsutsui M., Takahashi K.
  • Organizer: 16^<th> World Congress on Basic and Clinical Pharmacology
  • Place of Presentation: Copenhagen
  • Year and Date: 2010-07-20
• [Presentation] Stimulation of Noradrenaline Transporter and Serotonin Transporter Activity by Soy Phytoestrogen Genistein (2010)
  • Author(s): Nobuyuki Yanagihara
  • Organizer: 16^<th> World Congress on Basic and Clinical Pharmacology
  • Place of Presentation: Bella Center(Copenhagen, Denmark)
  • Year and Date: 2010-07-20
• [Presentation] Effects of nobiletin, one of citrus polymethoxy flavone, on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells (2010)
  • Author(s): Yanagihara N., Zhang H., Toyohira Y., Ueno S.
  • Organizer: 40^<th> Annual Meeting Society For Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2010-03-18
• [Presentation] Daul effects of nobiletin, a citrus polymethoxy flaon catecholamine secretion in culturebovine adrenal medullary cells (2010)
  • Author(s): Zhang H., Toyohira Y., Ueno S., Tsutsui M., Yamakuni T., Takahashi K., Yanagihara N.
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-17
• [Presentation] Daul effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells (2010)
  • Author(s): Zhang H., Toyohira Y., Ueno S., Tsutsui M., Yamakuni T., Takahashi K., Yanagihara N.
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-03-17
• [Presentation] Anxiety behavior in mice lacking all three isoforms of nitric oxide synthase (2010)
  • Author(s): Ueno S., Tsutsui M., Yoshimura R., Toyohira Y., Nakamura J., Shimokawa H., Yanagihara N.
  • Organizer: 第83回日本薬理学会年会(シンポジウム)
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-03-16
• [Presentation] Effects of nobiletin, a polymethoxy flavone, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. (2009)
  • Author(s): Zhang H., Toyohira Y., Shinohara Y., Ueno S., Tsutsui M., Yamakuni T., Takahashi K., Yanagihara N.
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-03-18
• [Presentation] Effects of phytoestrogens on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells. (2008)
  • Author(s): Yanagihara N., Shinohara Y., Toyohira Y., liu M., Ueno S., Tsutsui M., Zhang H.
  • Organizer: 第6回国際中医薬学大会
  • Place of Presentation: 天津市、中国
  • Year and Date: 2008-11-05
• [Book] 気をつけておくべき薬剤と食品・栄養剤との相互作用(下田妙子編集)(高齢者の栄養管理ガイドブック) (2010)
  • Author(s): 柳原延章
  • Total Pages: 135
  • Publisher: 文光堂
• [Book] 高齢者の栄養管理ガイドブック(下田妙子編集):気をつけておくべき薬剤と食品・栄養剤との相互作用 (2010)
  • Author(s): 柳原延章
  • Total Pages: 135
  • Publisher: 文光堂