Elucidation of the Function and Physiological Role of a Novel Polyamine Transporter

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Nagoya City University
• Principal Investigator: Hiroaki Yuasa 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (20191471)
• Co-Investigator(Kenkyū-buntansha): 保嶋 智也 名古屋市立大学, 医薬学総合研究院(薬学), 講師 (50753555) ; 山城 貴弘 名古屋市立大学, 医薬学総合研究院(薬学), 助教 (20826614)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: トランスポーター / ポリアミン / スペルミジン / スペルミン / プトレシン / 前立腺 / 薬物送達 / 創薬標的

Outline of Final Research Achievements

We could make a progress in elucidating the molecular function of PAMT1 as a newly found transporter for polyamines. In addition, in the evaluation of the tissue distribution of PAMT1 (mRNA), PAMT1 was found to be specifically expressed in the prostate. Although we could not fully demonstrate the functional expression of PAMT1 in prostate-derived model cell lines such as the LNCaP cell, PAMT1 expression was found to be increased by androgens, suggesting that PAMT1 may play a physiological role as a plolyamine transporter under the conditions in which it is induced by androgens. As related research outcomes, we newly found the orotate transport function of OAT10 and a few other transporters. We also found another novel polyamine transporter candidate.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

PAMT1の機能特性及び関連情報の把握は、PAMT1を介した薬物送達、PAMT1を標的としたポリアミン関連疾患治療薬の開発、PAMT1の機能変動を踏まえたポリアミン関連疾患治療法の考案等の可能性に向けた応用取組みのための基盤として重要である。本研究では、そのような応用へ向けての基礎的な情報集積を図るものとしての成果を挙げることができた。