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 language | English |
|---|---|
| Pages (from-to) | 1456-1463 |
| Number of pages | 8 |
| Journal | Molecular Nutrition and Food Research |
| Volume | 56 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2012 Sep |
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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 journal › Article
}
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 -