Identification of novel DOPA ligands and electrophysiological analysis of DOPA-induced response

• Project/Area Number: 20300132
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Yokohama City University
• Principal Investigator: GOSHIMA Yoshio Yokohama City University, 医学研究科, 教授 (00153750)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Takuya 横浜市立大学, 医学研究科, 教授 (20423824) ; YAGAMI Tatsuro 姫路独協大学, 薬学部, 教授 (00363812) ; KAJIWARA Yasuhiro 横浜市立大学, 国際総合科学部, 教授 (50275020) ; YURA Kei 独立行政法人日本原子力研究開発機構, 量子ビーム応用研究部門, 研究副主幹 (50252226)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2008: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 神経伝達物質 / 受容体 / 自律神経系 / ドーパ / 電気生理学 / 自律神経

Research Abstract

DOPA is a novel neurotransmitter candidate in the central nervous system. In an attempt to identify a specific receptor(s) for DOPA, we have searched for selective and stable DOPA ligands. We found a positive fraction in L-threo-dihydroxyphenyserine-containing solution to induce depressor and bradycardic response when microinjected into the nucleus tractus solitarii (NTS) of anesthetized rats. In multiple electrode array system, we also found biphasic response to DOPA in NTS area of rat brain stem slices. While conducting this project, we newly identified a receptor candidate for DOPA.

Research Products

• [Journal Article] 喫煙の生理学 (2010)
  • Author(s): 五嶋良郎
  • Journal Title: 臨床と研究 Pages: 743-746
• [Journal Article] Genes required for cellular UNC-6/netrin localization in Caenorhabditis elegans. (2010)
  • Author(s): Asakura T, Waga N, Ogura K, Goshima Y.
  • Journal Title: Genetics 185 Pages: 573-585
• [Journal Article] Computational analysis of the effects of antineoplastic agents on axonal transport. (2010)
  • Author(s): Goshima Y, Usui H, Shiozawa T, Hida T, Kuraoka S, Takeshita S, Yamashita N, Ichikawa Y, Kamiya Y, Gotoh T, Gotoh T.
  • Journal Title: J Pharmacol Sci. 114 Pages: 168-179
  • NAID: 10027746571
• [Journal Article] Genes required for cellular UNC-6/netrin localization in Caenorhabditis elegans. (2010)
  • Author(s): Asakura T, Waga N, Ogura K, Goshima Y.
  • Journal Title: Genetics Volume: 185 Pages: 573-585
  • Peer Reviewed
• [Journal Article] Computational analysis of the effects of antineoplastic agents on axonal transport. (2010)
  • Author(s): Goshima Y, Usui H, Shiozawa T, Hida T, Kuraoka S, Takeshita S, Yamashita N, Ichikawa Y, Kamiya Y, Gotoh T, Gotoh T.
  • Journal Title: J Pharmacol Sci Volume: 114 Pages: 168-179
  • NAID: 10027746571
  • Peer Reviewed
• [Journal Article] In vivo antagonism of the behavioral responses to L-3-,4-dihydroxyphenylalanine by L-3-,4-dihydroxyphenylalanine cyclohexyl ester in conscious rats. (2009)
  • Author(s): Matsushita N, Misu Y, Goshima Y.
  • Journal Title: Eur J Pharmacol. 605 Pages: 109-113
• [Journal Article] In vivo antagonism by L-3-,4-dihydroxyphenylalanine cyclohexyl ester against behavioral responses of conscious rats to L-3-,4-dihydroxyphenylalanine (2009)
  • Author(s): Matsushita N, Misu Y, Goshima Y.
  • Journal Title: Eur J Pharmacol 605 Pages: 109-113
  • Peer Reviewed
• [Journal Article] DOPA cyclohexyl ester, a DOPA antagonist, blocks the depressor responses elicited by microinjections of nicotine into the nucleus tractus solitarii of rats. (2008)
  • Author(s): Murota Y, Fujii M, Sugiyama Y, Funabashi T, Yagami T, Takahashi T, Goshima Y.
  • Journal Title: Neurosci Lett 442 Pages: 114-117
• [Journal Article] DOPA cyclohexyl ester, a DOPA antagonist, blocks the depressor responses elicited by micr (2008)
  • Author(s): Murota Y, Fujii M, Sugiyama Y, Funabashi T, Yagami T, Takahashi T, Gnshima Y
  • Journal Title: Neurosci Lett 42 Pages: 114-117
  • Peer Reviewed
• [Journal Article] In vivo antagonism of the behavioral responses to L-3-, 4-dihydroxyphenylalanine by L-3-, 4 (2008)
  • Author(s): Matsushita N, Misu Y, Goshima Y.
  • Journal Title: Eur J Pharmacol 605 Pages: 109-113
  • Peer Reviewed
• [Journal Article] Some DOPS redivatives mimic DOPAergic cardiovascular response in rats (2008)
  • Author(s): Fujii M, Murota Y, Yagami T, Aoki R, Kajiwara Y, Yamamoto N, Goshima Y.
  • Journal Title: Neurosci Res 61
• [Presentation] ドーパ関連リガンドの同定ならびにニコチン・ドーパ応答の解析 (2010)
  • Author(s): 五嶋良郎, 竹居光太郎, 中村史雄, 小倉顕一, 山下直也
  • Organizer: 喫煙科学財団研究発表会
  • Place of Presentation: 東京 京王プラザホテル
  • Year and Date: 2010-07-28
• [Presentation] Characterization of OA1, a novel L-3,4-dihydroxyphenylalanine(L-DOPA)receptor candidate (2010)
  • Author(s): Yamamoto T, Fujii M, Hiroshima Y, Yamashita N, Nakamura F, Goshima Y.
  • Organizer: 日本薬理学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-17
• [Presentation] ドーパ関連リガンドの同定ならびにニコチン・ドーパ応答の解析 (2010)
  • Author(s): 五嶋良郎, 竹居光太郎, 中村史雄, 小倉顕一, 山下直也
  • Organizer: 喫煙科学財団研究発表会
  • Place of Presentation: 東京
• [Presentation] 新規7回膜貫通型受容体DCAR-1は水溶性物質に対する忌避行動に関与する (2009)
  • Author(s): 青木令奈, 矢上達郎, 小倉顕一, 笹倉寛之, 宮前丈明, 中村史雄, 梶原康宏, 山本直毅, 森郁恵, 五嶋良郎
  • Organizer: 第82回薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] ラット孤束核のシナプス活動に対するL-DOPAの影響 (2009)
  • Author(s): 藤井桃, 室田裕大, 紙谷義孝, 五嶋良郎
  • Organizer: 第82回薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] Some DOPS derivatives mimic DOPAergic cardiovascular responses in rats. (2008)
  • Author(s): 藤井桃
  • Organizer: 日本神経科学大会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] Some DOPS derivatives mimic DOPAergic cardiovascular responses in rats. (2008)
  • Author(s): 藤井桃, 室田裕大, 矢上達郎, 青木令奈, 梶原康宏, 山本直毅, 五嶋良郎
  • Organizer: 第31回日本神経科学学会大会
  • Place of Presentation: 東京
• [Presentation] Chemical biology in C. elegans : a novel seven transmembrane domain receptor C06H5.7 mediates avoidance response to both volatile and water-soluble receptors in C. elegans. (2008)
  • Author(s): 青木令奈, 矢上達郎, 梶原康宏, 宮前丈明, 小倉顕一, 中村史雄, 笹倉寛之, 森郁恵, 五嶋良郎
  • Organizer: 第81回に本薬理学会年会
  • Place of Presentation: 横浜
• [Remarks] ホームページ等
  • URL: http://pharmac.med.yokohama-cu.ac.jp
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• [Remarks]
  • URL: http://pharmac.med.yokohama-cu.ac.jp
• [Remarks]
  • URL: http://pharmac.med.yokohama-cu.ac.jp