Elucidation of recognition mechanism of tetrodotoxin by puffer fish

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19195
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry and related fields
• Research Institution: Nagoya University
• Principal Investigator: Nishikawa Toshio 名古屋大学, 生命農学研究科, 教授 (90208158)
• Co-Investigator(Kenkyū-buntansha): 阿部 秀樹 名古屋大学, 生命農学研究科, 准教授 (90396804)
• Research Collaborator: Adachi Masaatsu
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: テトロドトキシン / フグ毒 / 誘引物質 / トリデオキシテトロドトキシン / フグ / EOG

Outline of Final Research Achievements

Because of the strong toxicity of tetrodotoxin (TTX), pufferfish uses TTX as a protective substance. On the other hand, there have been interesting reports that pufferfish are attracted to TTX. We thus first attempted to confirm that the TTX is actually sensed by the pufferfish olfactory organ by measuring an olfactory electrogram (EOG: electric field potential change generated when the olfactory epithelium is stimulated with an odorant). Unexpectedly, a strong EOG response was observed for 5,6,11-trideoxyTTX, a non-toxic analog of TTX rather than toxic TTX. We then synthesized several related compounds of the TTX analog for structure-activity relationship studies, and attempted behavior experiment using pufferfish, and to identify attractive olfactory cell species that receive the TTX analog.

Free Research Field

有機合成、天然物化学、ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究の最大の学術的意義は、これまでフグ誘引の活性の本体と考えられていたテトロドトキシン（TTX, フグ中毒の原因物質で猛毒）ではなく、無毒のTTX類縁体5,6,11-trideoxyTTXであることを初めて発見したことにある。この発見は、日本人に古くから馴染みの深いフグとフグが保有する毒素TTXの複雑な関係が、分子レベルで明らかになるきっかけとなるだろう。