Elimination of toxic substance through the activation of bitter taste receptosr

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21493
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Okayama University of Science
• Principal Investigator: Nakamura Motonao 岡山理科大学, 理学部, 教授 (40431762)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 苦味受容体 / GPCR / 皮膚細胞 / がん細胞 / 有害物質排出機構

Outline of Final Research Achievements

We confirmed the expressions of bitter taste receptors in human keratinocytes and various human cancer cells. These receptors were intracellularly localized in ER, but not in plasma membrane, and coupled with G12/13 type of G-proteins. Furthermore, we demonstrated the enhanced expression of ABC transporter type-B1 by the stimulation with bitter substances. When cancer cells were exposed to bitter substances for over 60 days, these cells exhibited resistance to anti-cancer drug compare with parental cells. There data suggest that in these cells, bitter taste receptors function as a sensor for toxic substances entered into cells, and activate the exclusion system to export the toxic substances to extracellular area.

Free Research Field

細胞生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

細胞内GPCRからの情報発信という新たなGPCR情報伝達の概念を立ち上げ、生体防御の観点からは苦味受容体を基軸とした新たな生体防御(有害物排除)機構を提唱する。また臨床への応用も期待できる。ガン治療時の抗ガン剤頻回投与で起こる耐性化は臨床的に大きな問題であるが、抗ガン剤を感受する苦味受容体の拮抗剤を創製すれば抗ガン剤耐性を回避できる。皮膚組織に侵入した有害物を苦味受容体が感受できず、排除低下で皮膚障害が起こるならば、苦味受容体の賦活剤による排除亢進で皮膚障害を抑制できる。本研究は，苦味受容体を創薬標的として捉えた点では全く前例のない研究である。