Search of new therapeutic agents for drug dependence and analysis of the inherited difference in patients with drug dependence.

• Project/Area Number: 20590269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kawasaki Medical School
• Principal Investigator: KATSURA Masashi Kawasaki Medical School, 薬学部・薬学科, 准教授 (80204452)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); 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: 薬物依存 / アルコール / L型高電位開口性カルシウムチャネル / 熱ショック蛋白 / 神経細胞 / 鉄代謝 / physical dependence / psychological dependence / L-type high voltage-gated Ca^<2+>channel / stored operated Ca^<2+>channel / morphine / alcohol / Fe^<2+>content / L-type high voltage-gated Ca^<2+> channel / heme oxygenase-1 / heat shock protein / stress marker / calcium channel subunit / drug dependence / L-type calcium channels / neuronal calcium sensor-1 / cerebrocortical neurons / HEp2 cells / transfection / transformation

Research Abstract

We investigated the detailed and new common mechanisms underling the accentuation of L-type high voltage-gated calcium channels function in establishment of psychological and physical dependence. Phosphorylation of heat shock factor and following increase in heat shock proteins 70 (HSP70) were observed in sustained ethanol-treated neuronal cells. In addition, intracellular ferrous iron concentrations were also significant increased after long-term exposure of ethanol. These results suggest the possibility that increase in intracellular HSP70 expressions and ferrous iron concentrations are new target for mechanism of drug dependence.

Research Products

• [Journal Article] Alcohol-induced hypoglycemia : Evidence for direct activation of L-type voltage-gated calcium channels and ryanodine receptors in pancreatic β cells. (2010)
  • Author(s): Katsura M, Shimoda M, Tatsumi F, Tawaramoto K, Shigeto M, Kaku K
  • Journal Title: Diabetes 59
• [Journal Article] Molecular mechanism of antihypertensive azelnidipine-induced augmention of insulin sensitivity : Evidence for antioxidative effect of insulin target 3T3-L1 cells. (2010)
  • Author(s): Tatsumi F, Katsura M, Hashiramoto M, Tawaramoto K, Hamamoto S, Shimoda M, Kanda Y, Matsuda M, Kaku K
  • Journal Title: Diabetes 59
• [Journal Article] パーキンソン病発症に関わる新たな因子:4E-BP (2010)
  • Author(s): 桂昌司
  • Journal Title: ファルマシア 63 Pages: 365-368
  • NAID: 110009867788
• [Journal Article] パーキンソン病発症に関わる新たな因子:4E-BP (2010)
  • Author(s): 桂昌司
  • Journal Title: ファルマシア Volume: 63 Pages: 365-368
  • NAID: 110009867788
  • Peer Reviewed
• [Journal Article] Alcohol-induced hypoglycemia : Evidence for direct activation of L-type voltage-gated calcium channels and ryanodine receptors in pancreatic β cells. (2010)
  • Author(s): Katsura, M.
  • Journal Title: Diabetes Volume: 59
  • Peer Reviewed
• [Journal Article] Molecular mechanism of antihypertensive azelnidipine-induced augmention of insulin sensitivity : Evidence for antioxidative effect of insulin target 3T3-L1 cells. (2010)
  • Author(s): Tatsumi, F.
  • Journal Title: Diabetes Volume: 59
  • Peer Reviewed
• [Journal Article] パーキンソン病発症に関わる新たな因子:4E-BP (2010)
  • Author(s): 桂昌司
  • Journal Title: ファルマシア (In press)
  • NAID: 110009867788
• [Journal Article] Direct evidence for the up-regulation of Vps34 regulated by PKCg during short-term treatment with morphine. (2009)
  • Author(s): Shibasaki M, Kurokawa K, Katsura M, Ohkuma S
  • Journal Title: Synapse 63 Pages: 365-368
• [Journal Article] Direct evidence for the up-regulation of Vps34 regulated by PKCγ during short-term treatment with morphine (2009)
  • Author(s): Shibasaki, M.
  • Journal Title: Synapse 63 Pages: 365-368
  • Peer Reviewed
• [Journal Article] Direct evidence for the up-regulation of Vps34 regulated by PKCγ during short-term treatment with morphine. (2009)
  • Author(s): Shibasaki, M.
  • Journal Title: Synapse 63 Pages: 365-368
  • Peer Reviewed
• [Journal Article] Low, but physiological, concentration of GLP-1 stimulates insulin secretion independent of the cAMP-dependent protein kinase pathway. (2008)
  • Author(s): Shigeto M, Katsura M, Matsuda M, Ohkuma S, Kaku K
  • Journal Title: J Pharmacol Sci. 108 Pages: 274-279
  • NAID: 10024592979
• [Journal Article] Low, but physiological, concentration of GLP-1 stimulates insulin secretion independent of the cAMP-dependent protein kinase pathway. (2008)
  • Author(s): Shigeto, M.
  • Journal Title: J. Pharmacol. Sci. 108 Pages: 274-279
  • Peer Reviewed
• [Presentation] 種々なストレス応答における熱ショック転写因子(HSF)の関与 (2010)
  • Author(s): 赤木玲子、太野路子、桂昌司、中井彰、井上幸江
  • Organizer: 第5回臨床ストレス応答学会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-20
• [Presentation] Alcohol-induced hypoglycemia : Evidence for direct activation of L-type voltage-gated calcium channels and ryanodine receptors in pancreatic β cells. (2010)
  • Author(s): Katsura M., Shimoda M., Tatsumi F., Tawaramoto K., Shigeto M., Kaku K.
  • Organizer: American Diabetes Association 70^<th> Scientific Sessions.
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2010-06-28
• [Presentation] Molecular mechanism of antihypertensive azelnidipine-induced augmention of insulin sensitivity : Evidence for antioxidative effect of insulin target 3T3-L1 cells. (2010)
  • Author(s): Tatsumi F., Katsura M., Hashiramoto M., Tawaramoto K., Hamamoto S., Shimoda M., Kanda Y., Matsuda M., Kaku K.
  • Organizer: American Diabetes Association 70^<th> Scientific Sessions.
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2010-06-26
• [Presentation] 脂肪細胞におけるジヒドロピリジンによる酸化ストレス抑制作用3T3-L1脂肪細胞を用いた検討 (2010)
  • Author(s): 辰巳文則、桂昌司、柱本満、俵本和仁、濱本純子、下田将司、菅田友紀子、松田昌文、加来浩平
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Presentation] グルタミンによる消化管保護効果発現のメカニズム (2010)
  • Author(s): 赤木玲子、太野路子、桂昌司、中井彰、井上幸江
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口
  • Year and Date: 2010-05-14
• [Presentation] ストレス負荷による消化管障害に対するグルタミンの保護効果 (2010)
  • Author(s): 赤木玲子、太野路子、桂昌司、中井彰、井上幸江
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] ストレス負荷による消化管障害に対するグルタミンの保護作用 (2010)
  • Author(s): 赤木玲子
  • Organizer: 日本薬学回第103年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] Methamphetamine誘発精神依存形成機構における高電位開口性カルシウムチャネル(HVCCs)α2/δ subunitの役割. (2008)
  • Author(s): 芝崎真裕
  • Organizer: 第43回日本アルコール・薬物医学会総会.
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-18
• [Presentation] Methamphetamine誘発精神依存形成機構における高電位開口性カルシウム チャネル(HVCCs)α2/δ subunitの役割 (2008)
  • Author(s): 芝崎真裕、黒川和宏、桂昌司、大熊誠太郎
  • Organizer: 第43回日本アルコール薬物医学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-16
• [Book] 安全性薬理試験マニュアル(安東賢太郎、橋本敬太郎,藤森観之助編)(第4節 抗喘息薬) (2009)
  • Author(s): 大熊誠太郎、芝崎真裕、桂昌司
  • Publisher: エル・アイ・シー
• [Book] 安全性薬理試験マニュアル「第4節抗喘息薬」(分担執筆) (2009)
  • Author(s): 大熊誠太郎
  • Total Pages: 432
  • Publisher: エル・アイ・シー
• [Book] アルコール・医学医療の最前線別冊(竹井謙之編集)(アルコール依存症病態発現時の神経薬理学的機序) (2008)
  • Author(s): 桂昌司、大熊誠太郎
  • Publisher: 医学のあゆみ
• [Book] 「アルコール依存症病態発現時の神経薬理学的機序」アルコール・医学医療の最前線別冊 医学のあゆみ(竹井謙之編集) (2008)
  • Author(s): 桂 昌司
  • Total Pages: 206
  • Publisher: 医歯薬出版