Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents

Tomomi Kagebayashi, Noriyasu Kontani, Yuko Yamada, Takafumi Mizushige, Toshinobu Arai, Kuniki Kino, Kousaku Ohinata

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    Abstract

    Scope: We found that a dipeptide, Arg-Phe (RF), had vasorelaxing activity in mesenteric artery isolated from spontaneously hypertensive rats (SHRs) (EC50 = 580 nM). We then investigated its mechanism of action, and elucidated its physiological functions. Methods and results: Vasorelaxing activities of RF-related peptides were tested. The retro-sequence dipeptide FR was inactive, suggesting that the RF sequence is important for a potent vasorelaxing effect. RA and AF were also inactive. RF-nh2 had vasorelaxing activity, implying that the C-terminal amidation of RF is tolerated. Nitric oxide (NO) and prostaglandins (PGs) are known to be vasorelaxing factors; however, the vasorelaxing activity of RF was inhibited by neither NG-nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor, nor indomethacin, a COX inhibitor. Interestingly, the activity was blocked by lorglumide, an antagonist of the cholecystokinin (CCK)1 receptor; however, RF had no affinity for CCK receptors, suggesting that RF stimulates CCK release. Orally administered RF decreased blood pressure in SHRs, and this antihypertensive activity was also blocked by a CCK1 antagonist. RF had CCK-like suppressive effects on food intake and gastrointestinal transit. RF increased intracellular Ca2+ flux and CCK release in enteroendocrine STC-1 cells. Conclusion: A novel CCK-dependent vasorelaxing RF decreases both blood pressure and food intake.

    Original languageEnglish
    Pages (from-to)1456-1463
    Number of pages8
    JournalMolecular Nutrition and Food Research
    Volume56
    Issue number9
    DOIs
    Publication statusPublished - 2012 Sep

    Fingerprint

    cholecystokinin
    dipeptides
    Dipeptides
    Cholecystokinin
    blood pressure
    food intake
    Rodentia
    rodents
    Eating
    Cholecystokinin Receptors
    Blood Pressure
    Inbred SHR Rats
    Gastrointestinal Transit
    antagonists
    Mesenteric Arteries
    gastrointestinal transit
    mesenteric arteries
    antihypertensive effect
    Nitric Oxide Synthase
    Indomethacin

    Keywords

    • Blood pressure
    • Cholecystokinin
    • Dipeptide
    • Food intake
    • l-amino acid ligase
    • Vasorelaxation

    ASJC Scopus subject areas

    • Food Science
    • Biotechnology

    Cite this

    Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents. / Kagebayashi, Tomomi; Kontani, Noriyasu; Yamada, Yuko; Mizushige, Takafumi; Arai, Toshinobu; Kino, Kuniki; Ohinata, Kousaku.

    In: Molecular Nutrition and Food Research, Vol. 56, No. 9, 09.2012, p. 1456-1463.

    Research output: Contribution to journalArticle

    Kagebayashi, Tomomi ; Kontani, Noriyasu ; Yamada, Yuko ; Mizushige, Takafumi ; Arai, Toshinobu ; Kino, Kuniki ; Ohinata, Kousaku. / Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents. In: Molecular Nutrition and Food Research. 2012 ; Vol. 56, No. 9. pp. 1456-1463.
    @article{e5702cb45fcd406ba2fce0e7086ed6d6,
    title = "Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents",
    abstract = "Scope: We found that a dipeptide, Arg-Phe (RF), had vasorelaxing activity in mesenteric artery isolated from spontaneously hypertensive rats (SHRs) (EC50 = 580 nM). We then investigated its mechanism of action, and elucidated its physiological functions. Methods and results: Vasorelaxing activities of RF-related peptides were tested. The retro-sequence dipeptide FR was inactive, suggesting that the RF sequence is important for a potent vasorelaxing effect. RA and AF were also inactive. RF-nh2 had vasorelaxing activity, implying that the C-terminal amidation of RF is tolerated. Nitric oxide (NO) and prostaglandins (PGs) are known to be vasorelaxing factors; however, the vasorelaxing activity of RF was inhibited by neither NG-nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor, nor indomethacin, a COX inhibitor. Interestingly, the activity was blocked by lorglumide, an antagonist of the cholecystokinin (CCK)1 receptor; however, RF had no affinity for CCK receptors, suggesting that RF stimulates CCK release. Orally administered RF decreased blood pressure in SHRs, and this antihypertensive activity was also blocked by a CCK1 antagonist. RF had CCK-like suppressive effects on food intake and gastrointestinal transit. RF increased intracellular Ca2+ flux and CCK release in enteroendocrine STC-1 cells. Conclusion: A novel CCK-dependent vasorelaxing RF decreases both blood pressure and food intake.",
    keywords = "Blood pressure, Cholecystokinin, Dipeptide, Food intake, l-amino acid ligase, Vasorelaxation",
    author = "Tomomi Kagebayashi and Noriyasu Kontani and Yuko Yamada and Takafumi Mizushige and Toshinobu Arai and Kuniki Kino and Kousaku Ohinata",
    year = "2012",
    month = "9",
    doi = "10.1002/mnfr.201200168",
    language = "English",
    volume = "56",
    pages = "1456--1463",
    journal = "Molecular Nutrition and Food Research",
    issn = "1613-4125",
    publisher = "Wiley-VCH Verlag",
    number = "9",

    }

    TY - JOUR

    T1 - Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents

    AU - Kagebayashi, Tomomi

    AU - Kontani, Noriyasu

    AU - Yamada, Yuko

    AU - Mizushige, Takafumi

    AU - Arai, Toshinobu

    AU - Kino, Kuniki

    AU - Ohinata, Kousaku

    PY - 2012/9

    Y1 - 2012/9

    N2 - Scope: We found that a dipeptide, Arg-Phe (RF), had vasorelaxing activity in mesenteric artery isolated from spontaneously hypertensive rats (SHRs) (EC50 = 580 nM). We then investigated its mechanism of action, and elucidated its physiological functions. Methods and results: Vasorelaxing activities of RF-related peptides were tested. The retro-sequence dipeptide FR was inactive, suggesting that the RF sequence is important for a potent vasorelaxing effect. RA and AF were also inactive. RF-nh2 had vasorelaxing activity, implying that the C-terminal amidation of RF is tolerated. Nitric oxide (NO) and prostaglandins (PGs) are known to be vasorelaxing factors; however, the vasorelaxing activity of RF was inhibited by neither NG-nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor, nor indomethacin, a COX inhibitor. Interestingly, the activity was blocked by lorglumide, an antagonist of the cholecystokinin (CCK)1 receptor; however, RF had no affinity for CCK receptors, suggesting that RF stimulates CCK release. Orally administered RF decreased blood pressure in SHRs, and this antihypertensive activity was also blocked by a CCK1 antagonist. RF had CCK-like suppressive effects on food intake and gastrointestinal transit. RF increased intracellular Ca2+ flux and CCK release in enteroendocrine STC-1 cells. Conclusion: A novel CCK-dependent vasorelaxing RF decreases both blood pressure and food intake.

    AB - Scope: We found that a dipeptide, Arg-Phe (RF), had vasorelaxing activity in mesenteric artery isolated from spontaneously hypertensive rats (SHRs) (EC50 = 580 nM). We then investigated its mechanism of action, and elucidated its physiological functions. Methods and results: Vasorelaxing activities of RF-related peptides were tested. The retro-sequence dipeptide FR was inactive, suggesting that the RF sequence is important for a potent vasorelaxing effect. RA and AF were also inactive. RF-nh2 had vasorelaxing activity, implying that the C-terminal amidation of RF is tolerated. Nitric oxide (NO) and prostaglandins (PGs) are known to be vasorelaxing factors; however, the vasorelaxing activity of RF was inhibited by neither NG-nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor, nor indomethacin, a COX inhibitor. Interestingly, the activity was blocked by lorglumide, an antagonist of the cholecystokinin (CCK)1 receptor; however, RF had no affinity for CCK receptors, suggesting that RF stimulates CCK release. Orally administered RF decreased blood pressure in SHRs, and this antihypertensive activity was also blocked by a CCK1 antagonist. RF had CCK-like suppressive effects on food intake and gastrointestinal transit. RF increased intracellular Ca2+ flux and CCK release in enteroendocrine STC-1 cells. Conclusion: A novel CCK-dependent vasorelaxing RF decreases both blood pressure and food intake.

    KW - Blood pressure

    KW - Cholecystokinin

    KW - Dipeptide

    KW - Food intake

    KW - l-amino acid ligase

    KW - Vasorelaxation

    UR - http://www.scopus.com/inward/record.url?scp=84865760817&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84865760817&partnerID=8YFLogxK

    U2 - 10.1002/mnfr.201200168

    DO - 10.1002/mnfr.201200168

    M3 - Article

    VL - 56

    SP - 1456

    EP - 1463

    JO - Molecular Nutrition and Food Research

    JF - Molecular Nutrition and Food Research

    SN - 1613-4125

    IS - 9

    ER -