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Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1

Authors

  • Ikumi Tamai,

    1. Department of Pharmacobio-dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13–1 Takara-machi, Kanazawa 920-0934, Japan
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  • Takeo Nakanishi,

    1. Department of Pharmacobio-dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13–1 Takara-machi, Kanazawa 920-0934, Japan
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  • Haruki Nakahara,

    1. Department of Pharmacobio-dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13–1 Takara-machi, Kanazawa 920-0934, Japan
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  • Yoshimich Sai,

    1. Department of Pharmacobio-dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13–1 Takara-machi, Kanazawa 920-0934, Japan
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  • Vadivel Ganapathy,

    1. Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912.
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  • Frederick H. Leibach,

    1. Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912.
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  • Akira Tsuji

    Corresponding author
    1. Department of Pharmacobio-dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13–1 Takara-machi, Kanazawa 920-0934, Japan
    2. CREST, Japan Science and Technology Corporation, 4–1–8 Moto-machi, Kawaguchi 332-0012, Japan
    • Department of Pharmacobio-dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13–1 Takara-machi, Kanazawa 920-0934, Japan
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Abstract

In the present study, possible enhancement of intestinal absorption of L-dopa by utilizing intestinal peptide transporter was examined using Caco-2 cells and Xenopus oocytes expressing human peptide transporter (hPepT1). To see whether this peptide transporter could be utilized for the improvement of L-dopa absorption, we employed a dipeptide-mimetic derivative of L-dopa, L-dopa-L-Phe. L-Dopa-L-Phe inhibited the uptake of [14C]Gly-Sar, but not that of L-[3H]-dopa by Caco-2 cells. Uptake of L-dopa-L-Phe was increased by expression of hPepT1 in Xenopus oocytes. The appearance of L-dopa and its metabolite, dopamine, on the basolateral side of Caco-2 cells was significantly higher after addition of L-dopa-L-Phe than after that of L-dopa and was reduced by the presence of Gly-Sar on the apical side. These results indicate that the L-dopa-L-Phe is absorbed more efficiently than L-dopa and is taken up via the peptide transporter, but not via the amino acid transporter, demonstrating the possibility of targeting the peptide transporter as a means for improving intestinal absorption of peptide-like drugs.

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