Characterization of Ile-His-Arg-Phe, a novel rice-derived vasorelaxing peptide with hypotensive and anorexigenic activities

Authors

  • Noriyasu Kontani,

    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
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  • Ryo Omae,

    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
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  • Tomomi Kagebayashi,

    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
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  • Kentaro Kaneko,

    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
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  • Yuko Yamada,

    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
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  • Takafumi Mizushige,

    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
    2. Research Unit for Physiological Chemistry, C-PIER, Kyoto University, Kyoto, Japan
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  • Ryuhei Kanamoto,

    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
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  • Kousaku Ohinata

    Corresponding author
    1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
    • Correspondence: Dr. Kousaku Ohinata, Division of Food Bioscience and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611–0011, Japan

      E-mail: ohinata@kais.kyoto-u.ac.jp

      Fax: +81-774-38-3774

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Abstract

Scope

Recently, we found that dipeptide Arg-Phe (RF) had cholecystokinin (CCK)-dependent vasorelaxing activity. The RF sequence is often observed in the primary structure of natural food proteins. In the current study, we investigated enzymatic conditions for the release of RF-related peptides from rice glutelin, a major storage protein, using gastrointestinal proteases. RF-related peptides were then characterized.

Methods and results

It was found that RF and Ile-His-Arg-Phe (IHRF) were released in the chymotrypsin digest of the partial structure of rice glutelin. We then focused on previously unidentified IHRF, corresponding to rice glutelin(155−158). IHRF had vasorelaxing activity in the mesenteric artery of spontaneous hypertensive rats (SHRs). Orally administered IHRF lowered systolic blood pressure in SHRs. The antihypertensive activity of IHRF was more potent and long-lasting than that of RF. IHRF-induced vasorelaxing activity was not blocked by inhibitors of nitric oxide synthase and cyclooxygenase, but by an antagonist for CCK1 receptor. IHRF also had CCK-like suppressive activities in food intake and gastrointestinal transit. IHRF increased intracellular Ca2+ flux and CCK release in the enteroendocrine cell STC-1.

Conclusion

IHRF, a novel CCK-dependent vasorelaxing peptide, decreases both blood pressure and food intake in rodents.

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