Role of receptor glycosylation on the effects of narcotic analgesics

• Project/Area Number: 22790518
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: 財団法人東京都医学総合研究所 (2011); Tokyo Metropolitan Organization for Medical Research (2010)
• Principal Investigator: KASAI Shinya 財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (20399471)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: オピオイド受容体 / 鎮痛薬 / オピオイド / 糖鎖修飾 / 遺伝子多型 / モデルマウス / ミューオピオイド受容体 / モルヒネ / 薬物感受性 / 糖鎖 / 遺伝子 / 脳・神経 / 細胞・組織 / 薬理学

Research Abstract

We established a congenic mouse strain(Oprm1^<HMI/HMI>) from wild-derived HMI inbred mice. The Oprm1^<HMI/HMI> congenic mice exhibited increased antinociception induced by morphine in the tail-flick and hot-plate tests. These data indicated that N-linked glycosylation of theμopioid receptor would influence the effects of opioid analgesics. The congenic mouse is useful strain for analyzing the effects of N-linked glycosylation of theμopioid receptor in vivo. The further studies with mutants of the N-linkedμopioid receptor glycosylation would absolutely contribute to the development of effective analgesics.

Research Products

• [Journal Article] Pharmacogenomics of the humanμ-opioid receptor (2011)
  • Author(s): Kasai S, Ikeda K
  • Journal Title: Pharmacogenomics Volume: 12 Pages: 1305-1320
  • Peer Reviewed
• [Journal Article] Inhibitory role of inducible cAMP early repressor(ICER) in methamphetamine-induced locomotor sensitization (2011)
  • Author(s): Han W, Takamatsu Y, Yamamoto H, Kasai S, Endo S, Shirao T, Kojima N, Ikeda K
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] Quantitative detection ofμopioid receptor : Western blot analyses usingμopioid receptor knockout mice (2011)
  • Author(s): Kasai S, Yamamoto H, Kamegaya E, Uhl GR, Sora I, Watanabe M, Ikeda K
  • Journal Title: Curr Neuropharmacol Volume: 9 Pages: 219-222
  • Peer Reviewed
• [Journal Article] Enhanced hyperthermia induced by MDMA in parkin knockout mice (2011)
  • Author(s): Takamatsu Y, Shiotsuki H, Kasai S, Iwamura T, Hattori N, Ikeda K
  • Journal Title: Curr Neuropharmacol Volume: 9 Pages: 96-99
  • Peer Reviewed
• [Journal Article] 野生由来近交系マウス系統におけるOprm1遺伝子多型とモルヒネ感受性の関連性 (2011)
  • Author(s): 笠井慎也,韓文華,畑春美,高松幸雄,萩野洋子,城石俊彦,小出剛,池田和隆
  • Journal Title: 日本神経精神薬理学雑誌 Volume: 31 Pages: 87-88
  • NAID: 10029094174
• [Journal Article] Reduced locomotor sensitization induced by methamphetamine and altered gene expression in ICER overexpressing mice (2011)
  • Author(s): Han W, Takamatsu Y, Kasai S, Endo S, Shirao T, Kojima N, Ikeda K
  • Journal Title: 日本神経精神薬理学雑誌 Volume: 31 Pages: 79-80
  • NAID: 10029094136
• [Journal Article] Quantitative detection of μ opioid receptor : Western blot analyses using μ opioid receptor knockout mice (2011)
  • Author(s): Shinya Kasai
  • Journal Title: Curr Neuropharmacol Volume: 9 Pages: 219-222
  • Peer Reviewed
• [Journal Article] Pharmacogenomics of the human μ-opioid receptor (2011)
  • Author(s): Shinya Kasai
  • Journal Title: Pharmacogenomics Volume: 12 Pages: 1305-1320
  • Peer Reviewed
• [Journal Article] Quantitative detection of μ opioid receptor : Western blot analyses using μ opioid receptor knockout mice. (2011)
  • Author(s): Kasai S
  • Journal Title: Curr Neuropharmacol Volume: 9 Pages: 219-222
  • Peer Reviewed
• [Journal Article] Essential role of NMDA receptor channel epsilon4 subunit(GluN2D) in the effects of phencyclidine, but not methamphetamine (2010)
  • Author(s): Hagino Y, Kasai S, Han W, Yamamoto H, Nabeshima T, Mishina M, Ikeda K
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] Association between 5-hydroxytryptamine 2A receptor gene polymorphism and postoperative analgesic requirements after major abdominal surgery (2010)
  • Author(s): Aoki J, Hayashida M, Tagami M, Nagashima M, Fukuda K, Nishizawa D, Ogai Y, Kasai S, Ikeda K, Iwahashi K
  • Journal Title: Neurosci Lett Volume: 479 Pages: 40-43
  • Peer Reviewed
• [Journal Article] 緩和医療～テーラーメイド医療の推進に向けて～ (2010)
  • Author(s): 笠井慎也
  • Journal Title: UP 2010-8 Volume: No.454 Pages: 19-23
  • NAID: 40017255080
• [Presentation] 外科的顎矯正手術におけるUGT2B7遺伝子多型とフェンタニル感受性の関連について神経化学I (2011)
  • Author(s): 村岡渡, 他
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京
  • Year and Date: 2011-10-28
• [Presentation] Association analysis between GIRK2 gene polymorphisms and postoperative analgesic requirements after painful cosmetic surgery (2011)
  • Author(s): Nishizawa D, et al
  • Organizer: 12th IGHG
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2011-10-14
• [Presentation] フェンサイクリジンの作用におけるNMDA受容体チャネルGluN2Dサブユニットの役割 (2011)
  • Author(s): 萩野洋子, 他
  • Organizer: 平成23年度アルコール・薬物依存関連学会合同学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] 日本人の喫煙歴と関連するOPRL1遺伝子多型の解析 (2011)
  • Author(s): 笠井慎也, 他
  • Organizer: 平成23年度アルコール・薬物依存関連学会合同学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-13
• [Presentation] シンポジウムS4-I-1,感覚から不快情動を生成する神経経路 (2011)
  • Author(s): 池田和隆, 他
  • Organizer: 第34回日本神経科学大会-こころの脳科学-
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-17
• [Presentation] Molecular mechanisms underlying the effects of phencyclidine (2011)
  • Author(s): Ikeda K, et al
  • Organizer: The Third Annual International Drug Abuse Research Society/International Society for Neurochemistry/ESN Satellite Meeting
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2011-08-23
• [Presentation] μ-Opioid receptor gene : Recent findings and future intervention approach (2011)
  • Author(s): Shinya Kasai
  • Organizer: 1st National Symposium of Biological Psychiatry and Psychopharmacology
  • Place of Presentation: Makassar, Indonesia(招待講演)
  • Year and Date: 2011-04-08
• [Presentation] μ-Opioid receptor gene : recent findings and future intervention approach (2011)
  • Author(s): Kasai S, et al
  • Organizer: 1st National Symposium of Biological Psychiatry and Psychopharmacology
  • Place of Presentation: Makassar, Indonesia
  • Year and Date: 2011-04-04
• [Presentation] Autism-like behaviors in mouse models of tuberous sclerosis complex and their recovery by rapamycin (2011)
  • Author(s): Sato A, et al
  • Organizer: The 2nd Meeting of Asian College of Neuropsychopharmacology
  • Place of Presentation: Seoul, Korea
• [Presentation] Association analysis between GIRK2 gene polymorphisms and opioid sensitivity (2011)
  • Author(s): Nishizawa D, et al
  • Organizer: The 2nd Meeting of Asian College of Neuropsychopharmacology
  • Place of Presentation: Seoul, Korea
• [Presentation] Association between GIRK3 gene polymorphisms and postoperative analgesic requirements after major abdominal surgery (2010)
  • Author(s): Nishizawa D, et al
  • Organizer: The American Society of Human Genetics 60th Annual Meeting
  • Place of Presentation: Washington DC
  • Year and Date: 2010-11-03
• [Presentation] 口腔外科手術後の下歯槽神経知覚障害と関連する遺伝子多型の網羅的探索 (2010)
  • Author(s): 小林大輔, 他
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: さいたま
  • Year and Date: 2010-10-28
• [Presentation] 痛みや鎮痛薬に対する感受性とベータ1アドレナリン受容体遺伝子(ADRB1)多型との関連解析 (2010)
  • Author(s): 森山彩子, 他
  • Organizer: 第4回日本緩和医療薬学会年会
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-09-25
• [Presentation] 痛覚感受性個人差の遺伝要因 (2010)
  • Author(s): 池田和隆, 他
  • Organizer: 第4回日本緩和医療薬学会年会
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-09-25
• [Presentation] GIRKチャネルサブユニットGIRK3の遺伝子多型と開腹術後鎮痛との関連 (2010)
  • Author(s): 西澤大輔, 他
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台
  • Year and Date: 2010-09-17
• [Presentation] OPRM1 118A/G遺伝子多型とTemperament and Character Inventoryの関連研究 (2010)
  • Author(s): 青木淳, 他
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台
  • Year and Date: 2010-09-16
• [Presentation] オピオイド感受性に及ぼすミューオピオイド受容体遺伝子配列の影響 (2010)
  • Author(s): 笠井慎也, 他
  • Organizer: 第31回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2010-08-26
• [Presentation] Polymorphisms of the genes encoding the mu-opioid receptor and GIRK2(KCNJ6) are associated with postoperative opioid requirements (2010)
  • Author(s): Ikeda K, et al
  • Organizer: CINP 2010
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-07
• [Presentation] Associations between nucleotide sequence differences in the Oprm1 gene and sensitivity to morphine in wild-derived inbred mouse strains (2010)
  • Author(s): Kasai S, et al
  • Organizer: CINP 2010
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-07
• [Presentation] Reduced locomotor sensitization induced by methamphetamine and altered gene expressions in ICER over-expressing mice (2010)
  • Author(s): Han W, et al
  • Organizer: CINP 2010
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-07
• [Presentation] Associations between nucleotide sequence differences in the Oprm1 gene and sensitivity to morphine in wild-derived inbred mouse strains. (2010)
  • Author(s): Kasai S
  • Organizer: CINP2010
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-07
• [Book] 緩和医療:痛みの理解から心のケアまで (2010)
  • Author(s): 小川節郎,鈴木勉,池田和隆,下山直人,松島英介,笠井慎也
  • Total Pages: 190
  • Publisher: 東京大学出版会
• [Book] Acute Pain (2010)
  • Author(s): Koide T
  • Publisher: Nova Science Publishers