G-protein coupled receptors: functional selectivity and disease

• Project/Area Number: 22591008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokyo
• Principal Investigator: MAKITA Noriko 東京大学, 医学部附属病院, 助教 (60353455)
• Co-Investigator(Kenkyū-buntansha): IIRI Tarho 東京大学, 医学部附属病院, 特任講師 (90313022)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 受容体 / G タンパク質 / 機能選択性 / 疾患 / 制御 / G タンパク質共役受容体 / Gタンパク質 / Gタンパク質共役受容体

Research Abstract

We examined functional selectivity of GPCR signalings, focusing on analysis of disease and ligand action against GPCRs: action of autoantibody working selectively against calcium-sensing receptor, unique action of ligands against novel V2 receptor mutants causing partial nephrogenic diabetes insipidus, drugs targeting selective inactivation, and cross-talk of GPCR signalings.

Research Products

• [Journal Article] Attenuated desensitization of β-adrenergic receptor by water-soluble -nitrosamines that induce S-nitrosylation without NO release. (2013)
  • Author(s): Makita N, Kabasawa Y, Otani Y, Firman, Sato J, Hashimoto M, Nakaya M, Nishihara H, Nangaku M, Kurose H, Ohwada T, Iiri T.
  • Journal Title: Circ Res. Volume: 112 Pages: 327-34
  • Peer Reviewed
• [Journal Article] (2013)
  • Author(s): Makita N and Tiiri T.
  • Journal Title: Tyrosine kinase induced thyroid disorder-review and hypothesis Thyroid Volume: 23 Pages: 151-9
  • Peer Reviewed
• [Journal Article] Tyrosine Kinase Inhibitor-Induced Thyroid Disorders: A Review and Hypothesis (2013)
  • Author(s): Makita N and Iiri T.
  • Journal Title: Thyroid Volume: 23 Issue: 2 Pages: 151-159
  • DOI: 10.1089/thy.2012.0456
  • Peer Reviewed
• [Journal Article] Attenuated desensitization of b-adrenergic receptor by water-soluble N-nitrosamines that induce S-nitrosylation without NO release (2013)
  • Author(s): Noriko Makita*, Yoji Kabasawa*, Yuko Otani, Firman, Junichiro Sato, Makiko Hashimoto, Michio Nakaya, Hiroaki Nishihara, Masaomi Nangaku, Hitoshi Kurose, Tomohiko Ohwada, Taroh Iiri
  • Journal Title: Circ. Res Volume: 112 Issue: 2 Pages: 327-334
  • DOI: 10.1161/circresaha.112.277665
  • Peer Reviewed
• [Journal Article] V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists. (2012)
  • Author(s): Takahashi K, Makita N, Manaka K, Hisano M, Akioka Y, Miura K, Takubo N, Iida A, Ueda N, Hashimoto M, Fujita T, Igarashi T, Sekine T, Iiri T.
  • Journal Title: J Biol Chem. Volume: 287 Pages: 2099-106
  • Peer Reviewed
• [Journal Article] Iiri T Regulation of RhoA signaling by the cAMP-dependent phosphorylation of RhoGDIa (2012)
  • Author(s): Oishi A, Makita N, Sato J
  • Journal Title: J Biol Chem. Volume: 287 Issue: 46 Pages: 38705-15
  • DOI: 10.1074/jbc.m112.401547
  • Peer Reviewed
• [Journal Article] A novel compound heterozygous mutation of Gitelman's syndrome in Japan, as diagnosed by an extraordinary response of the fractional excretion rate of chloride in the trichlormethiazide loading test. (2012)
  • Author(s): Ueda K, Makita N, Kawarazaki H, Fujiwara T, Unuma S, Monkawa T, Hayashi M, Fujita T.
  • Journal Title: Intern Med. Volume: 51 Pages: 1549-53
  • NAID: 130002062153
  • Peer Reviewed
• [Journal Article] V2R mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists (2012)
  • Author(s): Takahashi K, Makita N, et al.
  • Journal Title: J.Biol.Chem Volume: 287 Issue: 3 Pages: 2099-2106
  • DOI: 10.1074/jbc.m111.268797
  • Peer Reviewed
• [Journal Article] Painful thyroiditis and subsequent atrophic hypothyroidim after cord blood transfusion. (2011)
  • Author(s): Makita N, Isojima T, Hiwatari M, Kitanaka S, Ida K and Iiri T.
  • Journal Title: Thyroid Volume: 21 Pages: 1157-8
  • Peer Reviewed
• [Journal Article] Iiri T Angiotensin receptor 1b (2011)
  • Author(s): Manaka K, Makita N
  • Journal Title: AfCS Nature The signaling gatewayMolecule Pages.
• [Journal Article] Painful thyroiditis and subacute atrophic hypothyroidism after cord blood transfusion (2011)
  • Author(s): Makita N, et al.
  • Journal Title: Thyroid Volume: 21 Issue: 10 Pages: 1157-1158
  • DOI: 10.1089/thy.2010.0352
  • Peer Reviewed
• [Journal Article] Angiotensin receptor 1b (2011)
  • Author(s): Manaka K, Makita N, et al.
  • Journal Title: AfCS Nature Volume: (online)
  • Peer Reviewed
• [Journal Article] Iiri T.Sunitinib induces hypothyroidism with a markedly reduced vascularity. (2010)
  • Author(s): Makita N, Miyakawa M, Fujita T
  • Journal Title: Thyroid Volume: 20 Pages: 323-6
  • Peer Reviewed
• [Journal Article] Long-term clinical course of IgG4-related systemic disease accompanied by hypophysitis. (2010)
  • Author(s): Hori M, Makita N, Andoh T, Takiyama H, Yajima Y, Sakatani T, Fukumoto S, Iiri T, Fujita T.
  • Journal Title: Endocr J. Volume: 57 Pages: 485-92
  • NAID: 10029585054
  • Peer Reviewed
• [Journal Article] Erdheim-Chester disease: multisystem involvement and management with interferon-alpha. (2010)
  • Author(s): Suzuki HI, Hosoya N, Miyagawa K, Ota S, Nakashima H, Makita N, Kurokawa M.
  • Journal Title: Leuk Res. Volume: 34
  • Peer Reviewed
• [Journal Article] Sunitinib induces hypothyroidism with a markedly reduced vascularity (2010)
  • Author(s): Makita N, et al.
  • Journal Title: Thyroid Volume: 20 Pages: 323-326
  • Peer Reviewed
• [Journal Article] Long-term clinical course of IgG4-related systemic disease accompanied by hypophysiti (2010)
  • Author(s): Hori M, et al.
  • Journal Title: Endocrine J Volume: 57 Pages: 353-356
  • Peer Reviewed
• [Journal Article] カルシウム感知受容体-アロステリックな制御と疾患・薬剤 (2010)
  • Author(s): 槙田紀子、飯利太朗
  • Journal Title: 医学のあゆみ Volume: 233 Pages: 773-783
• [Presentation] 受容体シグナル調節機構とその分子異常を基盤とする疾患メカニズムの解明 (2013)
  • Author(s): 槙田紀子
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Year and Date: 2013-04-26
• [Presentation] 受容体シグナル調節機構とその分子異常を基盤とする疾患メカニズムの解明 (2013)
  • Author(s): 槙田紀子
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター
  • Invited
• [Presentation] カルシウム感知受容体と自己抗体 -biased signaling and allostery (2012)
  • Author(s): 飯利太朗、槙田紀子、佐藤潤一郎
  • Organizer: 第85回日本 生化学会(招待講演)
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15
• [Presentation] 著明な高カルシウム血症を呈し後天性低カルシウム尿性高カルシウム血症(AHH)において発見された自己 抗体の解析と治療 (2012)
  • Author(s): 槙田紀子、安藤隆雄、佐藤潤一郎、間中 勝則、村上聡子、堀江一郎、大石篤郎、 矢嶋由紀、橋本真紀子、川上純、藤田敏 郎、飯利太朗
  • Organizer: 第85回日本内分泌学 会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-04-22
• [Presentation] Gタンパク質共役受容体の新しいパラダイム-Biased signaling andallostery (2012)
  • Author(s): 飯利太朗
  • Organizer: 第85回日本薬理学会年次総会(招待講演)
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] Gタンパク質共役受容体の新しいパラダイム-Biased signaling and allostery (2012)
  • Author(s): 飯利太朗
  • Organizer: 日本薬理学会
  • Place of Presentation: 京都国際会館(招待講演)
  • Year and Date: 2012-03-14
• [Presentation] 著明な高カルシウム血症を呈し後天性低カルシウム尿性高カルシウム血症(AHH)において発見された自己抗体の解析と治療 (2012)
  • Author(s): 槙田紀子
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] カルシウム感知受容体と自己抗体-biased signalling and allostery (2012)
  • Author(s): 飯利太朗
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場
  • Invited
• [Presentation] 部分腎性尿崩症とV2受容体変異-リガンドの新規作用機構と治療への展望 (2011)
  • Author(s): 槙田紀子
  • Organizer: 第84日本内分泌学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2011-04-22
• [Presentation] Vasopressin V2 receptor mutants in partial nephrogenic diabetes insipidus (2011)
  • Author(s): Iiri T, Makita N.
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura(USA)
  • Year and Date: 2011-01-10
• [Presentation] Vasopressin V2 receptor mutants in partial nephrogenic diabetes insipidus (2011)
  • Author(s): Iiri T, et al.
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura, USA
  • Year and Date: 2011-01-10
• [Presentation] 部分腎性尿崩症と V2 受容体変異-リガンドの新規作用機構と治療への展望 (2011)
  • Author(s): 槙田紀子、間中勝則、佐藤潤一郎、大石篤郎、矢嶋由紀、橋本真紀子、関根孝司、 藤田敏郎、飯利太朗
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
• [Book] 最新内科学-甲状腺総論 (2012)
  • Author(s): 槙田紀子
  • Publisher: 西村書店
• [Book] 最新内 科学-甲状腺中毒症 (2012)
  • Author(s): 槙田紀子、飯利太朗
  • Publisher: 西村書店
• [Book] 泌尿器外科、分子標的薬の副作用マネジメントのコツ (2012)
  • Author(s): 槙田紀子、飯利太朗
  • Publisher: 医学図書出版
• [Book] 甲状腺総論 (2012)
  • Author(s): 槙田紀子
  • Publisher: 西村書店
• [Book] 甲状腺中毒症 (2012)
  • Author(s): 槙田紀子
  • Publisher: 西村書店
• [Book] 医学のあゆみ、最新Gタンパク質共役受容体研究(総ページ数290) (2010)
  • Author(s): 飯利太朗、槙田紀子
  • Publisher: 医歯薬出版
• [Book] 最新G蛋白質共役受容体研究 (2010)
  • Author(s): 飯利太朗、槙田紀子
  • Total Pages: 29
  • Publisher: 医歯薬出版
• [Remarks]
  • URL: http://www.todai-jinnai.com/
• [Remarks] 東京大学医学部附属病院 腎臓・内分泌内科
  • URL: http://www.todai-jinnai.com/
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~kid-endo/a-3-12.html
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~kid-endo/a-3-12.html
• [Patent(Industrial Property Rights)] Gs 共役受容体に対する医薬品医候補 化合物をスクリーニン (2011)
  • Inventor(s): 飯利太朗、槙田紀子
  • Industrial Property Rights Holder: 飯利太朗、槙田紀子
  • Industrial Property Number: 2011-230569
  • Filing Date: 2011-11-20
  • Overseas
• [Patent(Industrial Property Rights)] βアドレナリン受容体医薬品候補化 (2010)
  • Inventor(s): 飯利太朗、槙田紀子
  • Industrial Property Rights Holder: 飯利太朗、槙田紀子
  • Industrial Property Number: 2010-241688
  • Filing Date: 2010-10-28
  • Overseas
• [Patent(Industrial Property Rights)] βアドレナリン受容体医薬品候補化 (2010)
  • Inventor(s): 飯利太朗・槙田紀
  • Industrial Property Rights Holder: 飯利太朗・槙田紀
  • Industrial Property Number: 2010-241688
  • Filing Date: 2010-10-28