Identification of novel equilibrative oligopeptide transporters that may regulate drug absorption in the gastrointestinal tract

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06694
• 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: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Higuchi Kei 東京薬科大学, 薬学部, 講師 (10625304)
• Co-Investigator(Kenkyū-buntansha): 井上 勝央 東京薬科大学, 薬学部, 教授 (50315892) ; 岸本 久直 東京薬科大学, 薬学部, 講師 (80723600)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オリゴペプチドトランスポーター / 消化管 / 側底膜

Outline of Final Research Achievements

Drug absorption from the gastrointestinal tract is regulated by the cell membrane permeability of the gastrointestinal epithelium. This study aims to identify novel equilibrative oligopeptide transporters (EOPTs) that express at the basolateral membrane of gastrointestinal epithelial cells and play a role in drug absorption. Therefore, we examined the transport function of a group of candidate molecules of EOPTs previously identified as novel oligopeptide transporters. As a result, candidates like EOPT1 and EOPT2 can transport oligopeptides and peptidomimetics. These molecules are expressed at the basolateral membrane of a polarized gastrointestinal epithelial cell line. When the model cells are cultured on the cell culture inserts, the expression of EOPT2 enhances the permeation of the substrate from the apical to the basal side. Some of these results have already been published in an international journal article.

Free Research Field

トランスポーター

Academic Significance and Societal Importance of the Research Achievements

本成果である小腸上皮細胞側底膜で機能する新規オリゴペプチドトランスポーターの同定は、生理的なオリゴペプチドの吸収機構を明らかにするという点で、栄養生理学的にも重要な意義があるだけでなく、消化管からのβ-ラクタム系抗生物質などの薬物の吸収動態の新規制御因子の同定という価値がある。オリゴペプチドを認識するトランスポーターの同定は創薬・創剤において、経口吸収性を高める上で有益であることから、近年着目されている経口ペプチド創薬・創剤においても重要な知見となりうると考えられる。