Research of novel regulatory mechanism of general anesthetics through receptor trafficking

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659735
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Hirosaki University
• Principal Investigator: UENO Shinya 弘前大学, 医学(系)研究科(研究院), 教授 (00312158)
• Co-Investigator(Kenkyū-buntansha): NIKAIDO Yoshikazu 弘前大学, 医学(系)研究科(研究院), 助教 (50613478)
• Co-Investigator(Renkei-kenkyūsha): FUKUZAWA Masashi 弘前大学, 農学生命科学部, 教授 (10231557) ; YAMADA Junko 弘前大学, 医学(系)研究科(研究院), 講師 (30334965) ; MIGITA Keisuke 弘前大学, 医学(系)研究科(研究院), 助教 (10352262) ; TOMIYAMA Masahiko 弘前大学, 医学(系)研究科(研究院), 客員研究員 (40311542)
• Project Period (FY): 2011 – 2012
• Keywords: 神経科学 / 薬理学 / 情報伝達 / 麻酔薬作用機序 / タンパク輸送

Research Abstract

Phospholipase C related, but catalytically inactive protein-1 (PRIP-1) plays a critical role in trafficking and phosphorylation of GABA-A receptor. We found that PRIP-1 KO mice showed abnormal distribution of GABA-A receptor, and that efficacy of general anesthetics in KO mice reduced in comparison to wild type. These results suggest that receptor trafficking is involved in the regulation of anesthetic action.

Research Products

• [Journal Article] Dysfunction of extrasynaptic GABAergic transmission in phospholipase C-related, but catalytically inactive protein 1 knockout mice is associated with an epilepsy phenotype (2012)
  • Author(s): Zhu, G. Yoshida, S. Migita, K. Yamada, J. Mori, F. Tomiyama, M. Wakabayashi, K. Kanematsu, T. Hirata, M. Kaneko, S. Ueno, S. Okada, M
  • Journal Title: J Pharmacol Exp Ther Volume: 340(3) Pages: 520-528
  • DOI: DOI:10.1124/jpet.111.182386
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22128345
  • Peer Reviewed
• [Journal Article] Drebrin immunoreactivity in the striatum of a rat model of levodopa-induced dyskinesia (2012)
  • Author(s): Nishijima,H. Arai,A. Kimura,T. Mori, F. Yamada, J. Migita, K. Wakabayashi,K. Baba, M. Ueno, S. Tomiyama, M
  • Journal Title: Neuropathology Volume: (Epub ahead of print)
  • DOI: DOI:10.1111/neup.12009
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23241013
  • Peer Reviewed
• [Journal Article] Phenotypes of pain behavior in phospholipase C-related but catalytically inactive protein type 1 knockout mice (2011)
  • Author(s): Migita,K. Tomiyama,M. Yamada, J. Fukuzawa, M. Kanematsu, T. Hirata, M. Ueno, S
  • Journal Title: Mol Pain Volume: 7 Pages: 79-86
  • DOI: DOI:10.1186/1744-8069-7-79
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22008183
  • Peer Reviewed
• [Presentation] PRIP-1ノックアウトマウスの痛覚異常は脊髄におけるGABA作動性シナプス伝達異常が関与している (2012)
  • Author(s): 右田啓介、冨山誠彦、山田順子、二階堂義和、兼松隆、平田雅人、上野伸哉
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 20120918-21
• [Presentation] Delayed induction of anesthesia by propofol in mice deficient in phospholipase C-related but catalytically inactive protein type-1 (2012)
  • Author(s): Nikaido Y, Yamada J, Migita K, Shiba Y, Kushikata T, Hirota K, Kanematsu T, Hirata M, Ueno S
  • Organizer: 8th FENS Forum of Neuroscience
  • Place of Presentation: Spain, Barcelona
  • Year and Date: 20120714-18
• [Presentation] PRIP-1 KOマウスにおけるプロポフォールの麻酔効果導入の遅延と効果維持の低下 (2012)
  • Author(s): 二階堂義和、太田純子、右田啓介、山田順子、柴佑子、櫛方哲也、廣田和美、兼松隆、平田雅人、上野伸哉
  • Organizer: 第19回日本静脈麻酔学会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-29
• [Presentation] TONIC GABAERGIC TRANMISSION IN BLA NEURONS (2011)
  • Author(s): Yamada J, Migita K, Shiba Y, Kanemnatsu T, Hirata M, Ueno S
  • Organizer: III International symposium "Interaction of nervous and immune systems in health and disease"
  • Place of Presentation: Saint Petersburg, Russia
  • Year and Date: 20110707-11
• [Presentation] Dysfunction of tonic GABAergic transmission in PRIP-1 KO mice (2011)
  • Author(s): Yamada J, Migita K, Shiba Y, Kanematsu T, Hirata M, Ueno S
  • Organizer: The 10th Korea-Japan Joint Symposium of Brain Sciences, and Cardiac and Smooth Muscle Sciences
  • Place of Presentation: Gyeongju Republic, Korea
  • Year and Date: 20110217-19
• [Remarks]
  • URL: http://www.med.hirosaki-u.ac.jp/~neurophysiol/