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Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents.
MedLine Citation:
PMID:  22945436     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
SCOPE: We found that a dipeptide, Arg-Phe (RF), had vasorelaxing activity in mesenteric artery isolated from spontaneously hypertensive rats (SHRs) (EC(50) = 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-nh(2) 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 N(G) -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 CCK(1) antagonist. RF had CCK-like suppressive effects on food intake and gastrointestinal transit. RF increased intracellular Ca(2+) flux and CCK release in enteroendocrine STC-1 cells.
CONCLUSION: A novel CCK-dependent vasorelaxing RF decreases both blood pressure and food intake.
Authors:
Tomomi Kagebayashi; Noriyasu Kontani; Yuko Yamada; Takafumi Mizushige; Toshinobu Arai; Kuniki Kino; Kousaku Ohinata
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Publication Detail:
Type:  Journal Article     Date:  2012-08-01
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  56     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1456-63     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
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