Long-term treatment with morphine increases the D-serine content in the rat brain and spinal cord by regulating the mRNA and protein expressions of serine racemase and D-amino acid oxidase

• Project/Area Number: 23592312
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Tokai University
• Principal Investigator: ITO Kenji 東海大学, 医学部, 講師 (10317779)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Masanobu 東海大学, 医学部, 准教授 (90276791)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: モルヒネ / 鎮痛耐性 / NMDA受容体 / D-セリン / Dセリン / 鎮痛 / 耐性 / 代謝 / 疼痛 / セリンラセマーゼ / Ｄアミノ酸酸化酵素 / 術後痛

Research Abstract

The expression of mRNA and protein of serine racemase and D-amino acid oxidase increased in forebrain and spinal cord of rats developing morphine torelance. The levels of D-serine in increased in forebrain and spinal cord of rats developing morphine torelance. These results demonstrated that elevated D-serine level in rats developing morphine torelance could at least in part be involved in the activation of NMDA receptor via glycine site.

Research Products

• [Journal Article] Potentiation of [Met5]enkephalin-induced antinociception by mixture of three peptidase inhibitors in rat (2014)
  • Author(s): Murata T, Yoshikawa M, Watanabe M, Takahashi S, Kawaguchi M, Kobayashi H, Suzuki T
  • Journal Title: J. Anesthesia Volume: 28 Issue: 5 Pages: 708-715
  • DOI: 10.1007/s00540-014-1819-5
  • Year and Date: 2014-04-05
  • Peer Reviewed
• [Journal Article] Antinociceptive effect of intracerebroventricular administration of d-serine on formalin-induced pain (2014)
  • Author(s): Ito M, Yoshikawa M, Ito K, Matsuda M, Jin X.L., Takahashi S, Kobayashi H, Suzuki T
  • Journal Title: J. Anesthesia Volume: 28(2) Pages: 228-234
  • Peer Reviewed
• [Journal Article] Antinociceptive effect of intracerebroventricular administration of d-serine on formalin-induced pain. (2014)
  • Author(s): Ito M, Yoshikawa M, Ito K, Matsuda M, Jin X.L., Takahashi S, Kobayashi H, Suzuki T
  • Journal Title: Journal of Anesthesia Volume: 28 Pages: 228-234
  • Peer Reviewed
• [Journal Article] Increase in antinociceptive effect of [Leu5]enkephalin after intrathecal administration of mixture of three peptidase inhibitors (2013)
  • Author(s): Miura, M, Yoshikawa M, Watanabe M, Takahashi S, Ajimi J, Ito K, Ito M, Kawaguchi M, Kobayashi H, Suzuki T
  • Journal Title: Tokai J Exp Clin Med Volume: 38 (2) Pages: 62-70
  • Peer Reviewed
• [Journal Article] Methamphetamine-withdrawal stress activates PACAP-DBI pathway in rat salivary gland, resulting in inhibition of salivary secretion (2013)
  • Author(s): Okubo M, Yoshikawa M, Shinomiya T, Kawaguchi M
  • Journal Title: Tokai J Exp Clin Med Volume: 38 (2) Pages: 55-61
  • Peer Reviewed
• [Journal Article] Increase in antinociceptive effect of [Leu5]enkephalin after intrathecal administration of mixture of three peptidase inhibitors (2013)
  • Author(s): Miura, M, Yoshikawa M, Watanabe M, Takahashi S, Ajimi J, Ito K, Ito M, Kawaguchi M, Kobayashi H, Suzuki T.
  • Journal Title: Tokai J Exp Clin Med Volume: 38 Pages: 62-70
  • Peer Reviewed
• [Journal Article] Pharmacological protection from radiation- and chemoradiation- induced oral mucositis (2012)
  • Author(s): Cotrim P. A, Yoshikawa M, Sunshine N. A, Zheng C, Sowers L. A, Thetford D. A, Cook J. A, Mitchell B. J, Baum J. B
  • Journal Title: International Journal of Radiation Oncology Biology and Physics Volume: 83 (4) Pages: 1284-1290
  • Peer Reviewed
• [Journal Article] Diazepam Enhances Production of Diazepam-Binding Inhibitor (DBI), a Negative Saliva Secretion Regulator, Localized in Rat Salivary Gland (2011)
  • Author(s): Tsukagoshi E, Kawaguchi M, Shinomiya T, Yoshikawa M, Kawano T, Okubo M, Sawaki K
  • Journal Title: J Pharmacol Sci Volume: 115 Pages: 221-229
  • NAID: 10029892190
• [Journal Article] Proteomic Analysis of Lipopolysaccharide- treated Submandibular Gland in Rat (2011)
  • Author(s): Sawaki K, Shinomiya T, Okubo M, Tsukagashi E, Ogane M, Matsuura M, Yoshikawa M, Kawaguchi M
  • Journal Title: Bulletin of Tokyo Dental College Volume: 52(1) Pages: 31-37
  • NAID: 130004868647
• [Journal Article] Effect of three peptidase inhibitors on antinociceptive potential and toxicity with intracerebroventricular administration of dynorphin A (1-17) or (1-13) in rat
  • Author(s): Ajimi J, Yoshikawa M, Takahashi S, Miura M, Tsukamoto H, Kawaguchi M, Kobayashi H, Suzuki T
  • Journal Title: J. Anesthesia Volume: (in press)
  • Peer Reviewed
• [Presentation] D-アミノ酸と唾液分泌 (2013)
  • Author(s): 吉川正信,大久保みぎわ,三次百合香,濱瀬健司,金野柳一,川口充
  • Organizer: D-アミノ酸研究会第9回学術講演会
  • Place of Presentation: 関西大学(大阪)
  • Year and Date: 2013-09-14
• [Presentation] D-methionine as a protector for irradiation-induced oral mucositis or salivary glands dysfunction (2013)
  • Author(s): 吉川正信,村山千恵子, Ana P. Cotrium,平山亮一,古澤佳也,塚田秀雄, Bruce J Baum
  • 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] D-アミノ酸と唾液腺 (2013)
  • Author(s): 吉川正信,大久保みぎわ,三次百合香,濱瀬健司,村山千恵子,金野柳一,川口充
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 東北大学(宮城)
  • Year and Date: 2013-03-19
• [Presentation] 放射線障害に対する防護薬としてのD体アミノ酸の可能性 (2013)
  • Author(s): 吉川正信,村山千恵子,古澤佳也,平山亮一,鵜澤玲子,松本謙一郎
  • Organizer: 第15回癌治療増感研究シンポジウム
  • Place of Presentation: 猿沢荘(奈良)
  • Year and Date: 2013-02-09
• [Presentation] X線・重粒子線照射による口腔粘膜障害・唾液腺機能障害に対するD-メチオニンの防護効果 (2012)
  • Author(s): 吉川正信,村山千恵子, Ana P. Cotrium,平山亮一,鵜澤玲子, Bruce J Baum,古澤佳也
  • Organizer: 第8回D-アミノ酸研究会学術集会
  • Place of Presentation: 滋賀医科大学(滋賀)
  • Year and Date: 2012-09-07
• [Presentation] 重粒子線照射による口腔粘膜障害および唾液腺機能障害に対するD-メチオニンの防護効果 (2012)
  • Author(s): 吉川正信,村山千恵子,平山亮一,鵜澤玲子,古澤佳也
  • Organizer: 第41回放射線による制癌シンポジウム
  • Place of Presentation: フェストーネ(沖縄)
  • Year and Date: 2012-06-30
• [Presentation] Oral mucositis resultiing from irradiation (2012)
  • Author(s): 吉川正信
  • Organizer: The 85th Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: 京都国際会館
• [Presentation] 放射線照射による口腔粘膜障害に対するD体メチオニンの防護効果 (2011)
  • Author(s): 吉川正信,村山千恵子, Ana P. Cotrium, Anastatia L. Sower, James B. Mitchell, Bruce J Baum
  • Organizer: 第31回日本歯科薬物療法学会
  • Place of Presentation: 幕張メッセ国際会議場(千葉)
  • Year and Date: 2011-06-24