A novel pH-dependent drug transporter in intestine and liver

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14962
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Toho University
• Principal Investigator: SASAKI Shotaro 東邦大学, 薬学部, 講師 (50780300)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: トランスポーター / オリゴペプチド / 有機アニオン / pH依存性 / プロトン共輸送

Outline of Final Research Achievements

In order to clarify the characterization of a pH-dependent transporter involved in the absorption of drugs, we evaluated the substrate specificities of H+-coupled oligopeptide transporter PEPT1 and H+-coupled organic anion transporter. It was revealed that exposure of PEPT1-expressing oocytes to several monocarboxylate compounds induced inward currents. However, carboxylate drugs such as statins and NSAIDs were not substrates of PEPT1. On the other hand, when we investigated the effect of various substrates/inhibitors for well-known organic anion transporters (OATs and OATPs) on pH-dependent organic anion transport, the substrate specificity of H+-coupled organic anion transporter was revealed to be different from those specificities of OATs and OATPs.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

本研究において、既知の有機アニオン輸送担体とは異なるpH依存性輸送担体が医薬品を認識し得ることが示された。この研究成果は、新たな薬物の送達法の立案や副作用発現機序の解明などにつながる薬物動態を考える上で重要な知見である。最適な体内動態を示す薬物のデザイン、薬物間相互作用の予測および回避戦略などに応用可能であり、今後の研究のさらなる展開が期待される。