2006 Fiscal Year Final Research Report Summary
The Application of 'Passport' and 'Gateway' Proteins to the Absorption, Distribution, Excretion and Delivery of Drugs
| Project/Area Number |
16390039
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
TSUJI Akira Graduate School of Natural Science and Technology, Professor, 自然科学研究科, 教授 (10019664)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Yukio Graduate School of Natural Science and Technology, Associate, 自然科学研究科, 助教授 (30251440)
KUBO Yoshiyuki Graduate School of Natural Science and Technology, Research Associate, 自然科学研究科, 助手 (20377427)
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| Project Period (FY) |
2004 – 2006
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| Keywords | transporter / pharmacokinetics / drug development / protein array / membrane scaffold protein |
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| Research Abstract |
Drug transporters are thought to be an important factor in drug absorption, distribution, excretion and delivery. Therefore, in this project, we studied drug transporters that act as the 'Passport' and 'Gateway' proteins in human body, and aimed to elucidate the mechanisms of substrate recognition and construct a system for high-through-put screening in drug developments.
As the harvests of this project, the hydrolysis function of intestinal oligopeptide transporter, PEPT1, was suggested. The hypothesis that transporters could act as metabolic enzymes is novel one in this field, and verifying with proteoliposomes will provide beneficial findings to develop the orally effective peptide-like drugs. Additionally, Octn2 was shown to be involved in the intestinal absorption of carnitine. This finding suggested that influx transporters, such as PEPT1 and PCTN2, also have important roles in the intestinal absorption of drugs, and that further intensive in vivo researches will be lead to the improvement of bioavailability in oral administrations. Furthermore, study on protein-protein interaction provided the information about regulation mechanisms for drug transporter. PDZ-K1, a membrane scaffold protein was clarified, to regulate or modify the expression, stability and activity of drug transporters. Therefore, it was suggested that transporters are physiologically governed via interactions with membrane scaffold proteins. Information obtained from this project lead to build up high-through-put screening. Xenopus laevis oocytes system expressed with transporters and membrane scaffold protein.
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