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 journalArticlepeer-review

30 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

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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