Prostaglandin receptor dimerization and its-targeted drug development

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22503
• 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: Kumamoto University
• Principal Investigator: Sugimoto Yukihiko 熊本大学, 大学院生命科学研究部(薬), 教授 (80243038)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: プロスタグランジン / プロスタノイド / 二量体化 / GPCR / 構造活性相関 / シグナル伝達 / 逆作動薬 / ω3脂肪酸

Outline of Final Research Achievements

In this study, we first examined the universality of PG receptor heterodimerization and found that mGluR1 does not dimerize with any of the PG receptors, while EP3, EP1 and FP dimerize between any two of them. Therefore, dimerization is considered to be specific to PG receptors. We found that the potency of the β-arrestin (βarr) activation system by the EP4 receptor is also PG carboxylic acid free >> methylated, indicating that dimerization of PG receptors is required not only for hetero receptor activation, but also for βarr activation.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、脂質のカルボン酸と脂質受容体の塩基性アミノ酸のイオン結合が、二量体化の安定性を向上させるだけでなく、多彩な細胞内シグナルの活性化に果たす役割の解明に繋がるものであり、脂質受容体を標的とした制御性低分子の創成に貢献するものである。