Studies on ligand-gated anion channels as targets for novel agrochemicals

• Project/Area Number: 26292031
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Plant protection science
• Research Institution: Shimane University
• Principal Investigator: Ozoe Yoshihisa 島根大学, 生物資源科学部, 教授 (80112118)
• Co-Investigator(Kenkyū-buntansha): 河野 強 鳥取大学, 農学部, 教授 (50270567) ; 松田 一彦 近畿大学, 農学部, 教授 (00199796)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: イオンチャネル / 創薬ターゲット / 農薬科学

Outline of Final Research Achievements

Stable production of food is an important subject on a global scale. Agrochemicals are agricultural materials essential for crop protection and make a substantial contribution to crop production. In this study, the function and characteristics of ligand-gated anion channels of insects and nematodes were examined to provide insights into their potentiality as the site of action of pest control chemicals. This study led to the identification of novel action mechanisms and the discovery of novel lead compounds and ion channels.

Research Products

• [Int'l Joint Research] University of Copenhagen(Denmark)
• [Int'l Joint Research]
• [Journal Article] Ion channels and GPCRs as targets for pest control (2017)
  • Author(s): 尾添嘉久
  • Journal Title: Japanese Journal of Pesticide Science Volume: 42 Issue: 1 Pages: 55-62
  • DOI: 10.1584/jpestics.W17-18
  • NAID: 130005995714
  • ISSN: 2187-0365, 2187-8692
• [Journal Article] Pharmacological characterization of histamine-gated chloride channels from the housefly Musca domestica (2017)
  • Author(s): Tomo Kita, Takahiro Irie, Kazuki Nomura, Fumiyo Ozoe, Yoshihisa Ozoe
  • Journal Title: Neurotoxicology Volume: 印刷中 Pages: 245-253
  • DOI: 10.1016/j.neuro.2016.04.019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Okaramine insecticidal alkaloids show similar activity on both exon 3c and exon 3b variants of glutamate-gated chloride channels of the larval silkworm, Bombyx mori (2017)
  • Author(s): Shogo Furutani, Makoto Ihara, Kenji Kai, Keiji Tanaka, David B. Sattelle, Hideo Hayashi, Kazuhiko Matsuda
  • Journal Title: Neurotoxicology Volume: 印刷中 Pages: 240-244
  • DOI: 10.1016/j.neuro.2016.05.002
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Electrophysiological characterization of ivermectin triple actions on Musca chloride channels gated by L-glutamic acid and γ-aminobutyric acid (2016)
  • Author(s): Toshinori Fuse, Tomo Kita, Yunosuke Nakata, Fumiyo Ozoe, Yoshihisa Ozoe
  • Journal Title: Insect Biochemistry and Molecular Biology Volume: 77 Pages: 78-86
  • DOI: 10.1016/j.ibmb.2016.08.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ivermectin modulation of pH-sensitive chloride channels in the silkworm larvae of Bombyx mori (2016)
  • Author(s): Yuri Nakatani, Shogo Furutani, Makoto Ihara, and Kazuhiko Matsuda
  • Journal Title: Pesticide Biochemistry and Physiology Volume: 126 Pages: 1-5
  • DOI: 10.1016/j.pestbp.2015.08.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthesis of photoreactive ivermectin B1a derivatives and their actions on Haemonchus and Bombyx glutamate-gated chloride channels (2015)
  • Author(s): Toshinori Fuse, Izumi Ikeda, Tomo Kita, Shogo Furutani, Hiromitsu Nakajima, Kazuhiko Matsuda, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Journal Title: Pesticide Biochemistry and Physiology Volume: 120 Pages: 82-90
  • DOI: 10.1016/j.pestbp.2014.10.017
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 4,5-Substituted 3-isoxazolols with insecticidal activity act as competitive antagonists of housefly GABA receptors (2015)
  • Author(s): Genyan Liu, Fumiyo Ozoe, Kenjiro Furuta, and Yoshihisa Ozoe
  • Journal Title: Journal of Agricultural and Food Chemistry Volume: 63 Issue: 28 Pages: 6304-6312
  • DOI: 10.1021/acs.jafc.5b01843
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Differential interactions of 5-(4-piperidyl)-3-isoxazolol analogues with insect γ-aminobutyric acid receptors leading to functional selectivity (2015)
  • Author(s): Genyan Liu, Bente Frolund, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Journal Title: Insect Biochemistry and Molecular Biology Volume: 66 Pages: 64-71
  • DOI: 10.1016/j.ibmb.2015.10.002
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Meroterpenoid chrodrimanins are selective and potent blockers of insect GABA-gated chloride channels (2015)
  • Author(s): Yan Xu, Shogo Furutani, Makoto Ihara, Yun Ling, Xinling Yang, Kenji Kai, Hideo Hayashi, and Kazuhiko Matsuda
  • Journal Title: PLoS One Volume: 10 Issue: 4 Pages: e0122629-e0122629
  • DOI: 10.1371/journal.pone.0122629
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthesis of 1,3-di- and 1,3,4-trisubstituted 1,6-dihydro-6-iminopyridazines as competitive antagonists of insect GABA receptors (2014)
  • Author(s): Mohammad Mostafizur Rahman, Genyan Liu, Kenjiro Furuta, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Journal Title: Journal of Pesticide Science Volume: 39 Issue: 3 Pages: 133-143
  • DOI: 10.1584/jpestics.D14-052
  • NAID: 130004677984
  • ISSN: 1348-589X, 1349-0923
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Competitive antagonism of insect GABA receptors by 4-substituted 5-(4-piperidyl)-3-isothiazolols (2014)
  • Author(s): Genyan Liu, Kenjiro Furuta, Hiromitsu Nakajima, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Journal Title: Bioorganic and Medicinal Chemistry Volume: 22 Issue: 17 Pages: 4637-4645
  • DOI: 10.1016/j.bmc.2014.07.021
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Exon 3 splicing and mutagenesis identify residues influencing cell surface density of heterologously-expressed silkworm (Bombyx mori) glutamate-gated chloride channels (2014)
  • Author(s): Shogo Furutani, Makoto Ihara, Yuri Nishino, Miki Akamatsu, Andrew K. Jones, David B. Sattelle, and Kazuhiko Matsuda
  • Journal Title: Molecular Pharmacology Volume: 86 Issue: 6 Pages: 686-895
  • DOI: 10.1124/mol.114.095869
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] GluCl a target of indole alkaloid okaramines: a 25 year enigma solved (2014)
  • Author(s): Shogo Furutani, Yuri Nakatani,Yuka Miura, Makoto Ihara, Kenji Kai, Hideo Hayashi, and Kazuhiko Matsuda
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 6190-6190
  • DOI: 10.1038/srep06190
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ターゲットに変異をもつDieldrin抵抗性昆虫に対する環状塩素系殺虫剤の作用 (2017)
  • Author(s): 高市成美，松田一彦，尾添嘉久，田中啓司
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大学（京都市）
  • Year and Date: 2017-03-20
• [Presentation] 選択的生物制御の道を拓くアグリケミカルバイオロジー (2017)
  • Author(s): 松田一彦
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大学（京都市）
  • Year and Date: 2017-03-19
  • Invited
• [Presentation] プレニル化インドールアルカロイドokaramine生合成におけるazetidine環合成酵素の同定 (2017)
  • Author(s): 加藤直樹，大髙潤之介，衣笠清美，古谷章悟，高橋俊二，松田一彦，長田裕之
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大学（京都市）
  • Year and Date: 2017-03-19
• [Presentation] カイコガpH感受性塩素チャネルの超多様化により生じる薬理学的特性の変化 (2017)
  • Author(s): 奥原大樹，伊原誠，松田一彦
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大学（京都市）
  • Year and Date: 2017-03-18
• [Presentation] ライム病を媒介するシカダニ（Ixodes scapularis）の抑制性グルタミン酸受容体のアゴニストおよびアンタゴニストプロフィールとokaramine類の活性発現機構 (2017)
  • Author(s): 古谷章悟，伊原誠，甲斐建次，林英雄，Kristin Lees，Freddie A. Partridge，Steven Buckingham，David B. Sattelle，松田一彦
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大学（京都市）
  • Year and Date: 2017-03-18
• [Presentation] BHC立体異性体とその関連化合物のGABAアンタゴニスト活性 (2017)
  • Author(s): 田中啓司，高市成美，尾添嘉久，松田一彦
  • Organizer: 日本農薬学会第42回大会
  • Place of Presentation: 愛媛大学（松山市）
  • Year and Date: 2017-03-08
• [Presentation] Dieldrin，Aldrin，Endrin，Isodrin，γ-BHC とその類縁体のGABAアンタゴニスト活性 (2017)
  • Author(s): 高市成美，松田一彦，尾添嘉久，赤松美紀，田中啓司
  • Organizer: 日本農薬学会第42回大会
  • Place of Presentation: 愛媛大学（松山市）
  • Year and Date: 2017-03-08
• [Presentation] グルタミン酸作動性塩素イオンチャネルのフルララネルとイベルメクチンに対する感受性を決定づけるアミノ酸残基 (2017)
  • Author(s): 中田侑之介，旭美穂，中平国光，尾添富美代，尾添嘉久
  • Organizer: 日本農薬学会第42回大会
  • Place of Presentation: 愛媛大学（松山市）
  • Year and Date: 2017-03-08
• [Presentation] 新規殺虫剤フルキサメタミド（グレーシア）に関する研究（第三報）作用機構解析 (2017)
  • Author(s): 旭美穂，中平国光，尾添嘉久
  • Organizer: 日本農薬学会第42回大会
  • Place of Presentation: 愛媛大学（松山市）
  • Year and Date: 2017-03-08
• [Presentation] インドールアルカロイド オカラミンの活性発現に関する研究：ターゲットの特性と結合部位 (2017)
  • Author(s): 古谷章悟，伊原誠，甲斐建次，林英雄，松田一彦
  • Organizer: 日本農薬学会第42回大会
  • Place of Presentation: 愛媛大学（松山市）
  • Year and Date: 2017-03-07
• [Presentation] 農芸化学の中の農薬化学 (2017)
  • Author(s): 尾添嘉久
  • Organizer: 支部創立15周年記念日本農芸化学会中四国支部第47回講演会（支部例会）
  • Place of Presentation: 島根大学（松江市）
  • Year and Date: 2017-01-28
  • Invited
• [Presentation] Design of competitive antagonists for insect GABA receptors (2016)
  • Author(s): Yoshihisa Ozoe, Genyan Liu, Mohammad Mostafizur Rahman
  • Organizer: 44th Symposium on Structure-Activity Relationship and 31st Assembly for Pesticide Design Research
  • Place of Presentation: 京都大学（京都市）
  • Year and Date: 2016-11-16
• [Presentation] Molecular and functional characterization of histamine-gated chloride channels from the housefly, Musca domestica (2016)
  • Author(s): Yoshihisa Ozoe
  • Organizer: XXV International Congress of Entomology
  • Place of Presentation: Orange County Convention Center (Orlando, FA, USA)
  • Year and Date: 2016-09-30
  • Int'l Joint Research / Invited
• [Presentation] 昆虫抑制グルタミン酸受容体に対するOkaramineの活性発現機構 (2016)
  • Author(s): 古谷章悟，伊原誠，甲斐建次，林英雄，松田一彦
  • Organizer: 日本農芸化学会関西支部大会（第496回講演会）
  • Place of Presentation: 滋賀県立大学（彦根市）
  • Year and Date: 2016-09-17
• [Presentation] Insect ligand-gated ion channels as targets for insecticides (2016)
  • Author(s): Kazuhiko Matsuda
  • Organizer: 252nd American Chemical Society National Meeting
  • Place of Presentation: Loews Philadelphia Hotel (Philadelphia, PA, USA)
  • Year and Date: 2016-08-23
  • Int'l Joint Research / Invited
• [Presentation] Ligand-gated chloride channels and phenolamine GPCRs as important targets of pest control chemicals (2016)
  • Author(s): Yoshihisa Ozoe
  • Organizer: 252nd American Chemical Society National Meeting
  • Place of Presentation: Loews Philadelphia Hotel (Philadelphia, PA, USA)
  • Year and Date: 2016-08-22
  • Int'l Joint Research / Invited
• [Presentation] 糸状菌が産生する昆虫制御物質オカラミンの活性発現機構に関する研究：選択的スプ ライシングによるターゲットの多様化と活性 (2016)
  • Author(s): 古谷章悟、甲斐建次、伊原誠、松田一彦
  • Organizer: 2016年度日本農芸化学会大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-29
• [Presentation] 4-(3-Biphenylyl)-5-(4-piperidyl)-3-isoxazolol, an effective orthosteric ligand of insect GABA receptors (2016)
  • Author(s): Genyan Liu, Bente Frolund, Yunosuke Nakata, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Organizer: 日本農薬学会第41回大会
  • Place of Presentation: 島根大学（島根県松江市）
  • Year and Date: 2016-03-19
• [Presentation] フルララネル，フィプロニルおよびイベルメクチンのグルタミン酸作動性塩素イオンチャネルに対する作用 (2016)
  • Author(s): 中田侑之介、旭美穂、中平国光、尾添富美代、尾添嘉久
  • Organizer: 日本農薬学会第41回大会
  • Place of Presentation: 島根大学（島根県松江市）
  • Year and Date: 2016-03-19
• [Presentation] グルタミン酸およびGABA作動性イオンチャネルに対する駆虫薬イベルメクチンの３作用 (2016)
  • Author(s): 布施利紀、喜多知、中田侑之介、尾添富美代、尾添嘉久
  • Organizer: 日本農薬学会第41回大会
  • Place of Presentation: 島根大学（島根県松江市）
  • Year and Date: 2016-03-19
• [Presentation] カイコガpH感受性塩素チャネルの発現変動と遺伝子産物の多様化 (2016)
  • Author(s): 奥原大樹、松田一彦、伊原誠、伊藤克彦
  • Organizer: 2016年度日本農芸化学会大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-19
• [Presentation] 有害生物防除ターゲットとしてのイオンチャネルとGPCR (2016)
  • Author(s): 尾添嘉久
  • Organizer: 日本農薬学会第41回大会
  • Place of Presentation: 島根大学（島根県松江市）
  • Year and Date: 2016-03-18
  • Invited
• [Presentation] Crucial interactions of insect GABA receptors leading to competitive antagonism (2015)
  • Author(s): Genyan Liu, Bente Frolund, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Organizer: 日本農芸化学会2015年度中四国・西日本支部合同大会
  • Place of Presentation: 愛媛大学（愛媛県松山市）
  • Year and Date: 2015-09-18
• [Presentation] Molecular pharmacology of homomeric UNC-49B channels from southern root-knot nematodes (2015)
  • Author(s): Yoshihisa Ozoe, Kazuki Nomura, Tomo Kita, and Fumiyo Ozoe
  • Organizer: 250th American Chemical Society National Meeting
  • Place of Presentation: Boston Park Plaza Hotel (Boston, MA, USA)
  • Year and Date: 2015-08-16
  • Int'l Joint Research / Invited
• [Presentation] Activation, potentiation, and antagonism of Musca GABA receptors by ivermectin (2015)
  • Author(s): Toshinori Fuse, Tomo Kita, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Organizer: 250th American Chemical Society National Meeting
  • Place of Presentation: Boston Park Plaza Hotel (Boston, MA, USA)
  • Year and Date: 2015-08-16
  • Int'l Joint Research
• [Presentation] 殺虫性インドールアルカロイドオカラミンの活性発現機構と選択性 (2015)
  • Author(s): 古谷章悟、中谷有里、伊原誠、甲斐建次、林英雄、松田一彦
  • Organizer: 2015年度日本農芸化学会大会
  • Place of Presentation: 岡山大学（岡山県岡山市）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 4-Aryl-5-carbamoyl-3-isoxazolols as novel competitive antagonists of housefly GABA receptors (2015)
  • Author(s): Genyan Liu, Fumiyo Ozoe, Kenjiro Fruta, and Yoshihisa Ozoe
  • Organizer: 日本農薬学会第４０回記念大会
  • Place of Presentation: 玉川大学（東京都町田市）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] サツマイモネコブセンチュウGABA受容体（Mi-UNC-49B）のリガンド応答 (2015)
  • Author(s): 野村和希、喜多知、河野強、佐藤忠章、小池一男、尾添富美代、尾添嘉久
  • Organizer: 日本農薬学会第４０回記念大会
  • Place of Presentation: 玉川大学（東京都町田市）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 環構造をもつメロテルペン化合物Chrodrimanin類の作用点 (2015)
  • Author(s): 古谷章悟、Xu Yan、伊原誠、甲斐建次、林英雄、松田一彦
  • Organizer: 日本農薬学会第４０回記念大会
  • Place of Presentation: 玉川大学（東京都町田市）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 糸状菌が産生する殺虫性二次代謝産物オカラミンの標的：25年間未解明の謎を解く (2014)
  • Author(s): 古谷章悟、中谷有里、三浦由夏、伊原誠、甲斐建次、林英雄、松田一彦
  • Organizer: 2014年度日本農芸化学会関西支部大会
  • Place of Presentation: 奈良先端科学技術大学院大学（奈良県生駒市）
  • Year and Date: 2014-09-19 – 2014-09-20
• [Presentation] 4-Aryl-5-(4-piperidyl)-3-isothiazolols act as novel competitive antagonists for insect GABA receptors (2014)
  • Author(s): Genyan Liu, Kenjiro Furuta, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Organizer: 13th IUPAC International Congress of Pesticide Chemistry at the 248th American Chemical Society National Meeting
  • Place of Presentation: Marriott Marquis (San Francisco, USA)
  • Year and Date: 2014-08-10 – 2014-08-14
• [Presentation] Synthesis of iminopyridazines and their potencies as competitive antagonists in insect GABA receptors (2014)
  • Author(s): Mohammad Mostafizur Rahman, Kenjiro Furuta, Fumiyo Ozoe, and Yoshihisa Ozoe
  • Organizer: 13th IUPAC International Congress of Pesticide Chemistry at the 248th American Chemical Society National Meeting
  • Place of Presentation: Marriott Marquis (San Francisco, USA)
  • Year and Date: 2014-08-10 – 2014-08-14
• [Presentation] Pharmacological and physiological roles of insect ligand-gated chloride channels (2014)
  • Author(s): Yoshihisa Ozoe
  • Organizer: 13th IUPAC International Congress of Pesticide Chemistry at the 248th American Chemical Society National Meeting
  • Place of Presentation: Marriott Marquis (San Francisco, USA)
  • Year and Date: 2014-08-10 – 2014-08-14
  • Invited
• [Presentation] GABA-gated chloride channel: Multiple target sites of insecticidal action (2014)
  • Author(s): Yoshihisa Ozoe
  • Organizer: 13th IUPAC International Congress of Pesticide Chemistry at the 248th American Chemical Society National Meeting
  • Place of Presentation: Marriott Marquis (San Francisco, USA)
  • Year and Date: 2014-08-10 – 2014-08-14
  • Invited
• [Presentation] Probing insect LGICs using selective ligands (2014)
  • Author(s): Kazuhiko Matsuda
  • Organizer: 13th IUPAC International Congress of Pesticide Chemistry at the 248th American Chemical Society National Meeting
  • Place of Presentation: Marriott Marquis (San Francisco, USA)
  • Year and Date: 2014-08-10 – 2014-08-14
  • Invited
• [Book] Discovery and Synthesis of Crop Protection Products (2016)
  • Author(s): Yoshihisa Ozoe et al.
  • Total Pages: 200
  • Publisher: American Chemical Society
• [Remarks] 島根大学生物資源科学部生命工学科
  • URL: http://www.ipc.shimane-u.ac.jp/seimei/lab/lsb4.html