Subunit-dependent modulation of 5-HT3 receptor by anticancer drugs

• Project/Area Number: 25861560
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Osaka University
• Principal Investigator: YUKIKO Nakamura 大阪大学, 医学(系)研究科(研究院), 助教 (90548083)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: セロトニン３受容体 / 抗癌剤 / 5-HT3 receptor / anticancer drug / セロトニン受容体 / 5-HT3受容体 / 嘔吐

Outline of Final Research Achievements

It has been shown that anti-cancer drug induces secretion of serotonin (5-HT) from small intestine which activates serotonin type 3 (5-HT3) receptor to cause nausea and vomiting. In general, antagonist for 5-HT3 receptor is used as anti-emetics during chemotherapy. Previously, we reported that anti-cancer drug irinotecan itself inhibits 5-HT-gated current through the homomeric 5-HT3 receptor. Therefore we focused frequently-used anticancer drug to examine its effect to 5-HT3 receptor. More than 25% anticancer drugs modified 5-HT3 receptor response. Our finding suggested that these anticancer drugs could affect to anti-emetic activities through 5-HT3 receptor.

Research Products

• [Journal Article] 5-HT3 receptor expression in the mouse vestibular ganglion (2014)
  • Author(s): Takimoto Y, Ishida Y, Nakamura Y, Kamakura T, Yamada T, Kondo M, Kitahara T, Uno A, Imai T, Horii A, Okazaki S, Nishiike S, Inohara H, Shimada S
  • Journal Title: Brain Res Volume: 1557 Pages: 74-82
  • DOI: 10.1016/j.brainres.2014.02.016
  • Peer Reviewed
• [Journal Article] The 5-HT3A receptor is essential for fear extinction. (2013)
  • Author(s): Kondo M, Nakamura Y, Ishida Y, Yamada T, Shimada S
  • Journal Title: Learn Mem Volume: 21 Issue: 1 Pages: 1-4
  • DOI: 10.1101/lm.032193.113
  • Peer Reviewed
• [Journal Article] Functional expression of TRPV1 and TRPA1 in rat vestibular ganglia (2013)
  • Author(s): Kamakura T, Ishida Y, Nakamura Y, Yamada T, Kitahara T, Takimoto Y, Horii A, Uno A, Imai T, Okazaki S, Inohara H, Shimada S
  • Journal Title: Neurosci Lett Volume: 552 Pages: 92-97
  • DOI: 10.1016/j.neulet.2013.07.019
  • Peer Reviewed
• [Journal Article] Subunit-dependent inhibition and potentiation of 5-HT3 receptor by the anticancer drug, topotecan” Journal of neurochemistry (2013)
  • Author(s): Yukiko Nakamura
  • Journal Title: Journal of neurochemistry Volume: 125(1) Issue: 1 Pages: 7-15
  • DOI: 10.1111/jnc.12146
  • Peer Reviewed
• [Presentation] 抗癌剤による5-HT3受容体への直接作用 (2014)
  • Author(s): 中村 雪子、石田 雄介、近藤 誠、島田 昌一
  • Organizer: 第119回日本解剖学会総会全国学術集会
  • Place of Presentation: 栃木
• [Presentation] Direct modulation of 5-HT3 receptor by anti-cancer drugs. (2013)
  • Author(s): Yukiko Nakamura, Yusuke Ishida, Makoto Kondo, Shoich Shimada
  • Organizer: 第56回日本神経化学会大会
  • Place of Presentation: 京都
• [Presentation] 抗鬱効果を発揮する内因性物質について (2013)
  • Author(s): 中村 雪子
  • Organizer: 第14回 ORIGIN 神経科学研究会 夏のワークショップ 2013
  • Place of Presentation: 岐阜