| Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents. | |
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MedLine Citation:
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PMID: 22945436 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tomomi Kagebayashi; Noriyasu Kontani; Yuko Yamada; Takafumi Mizushige; Toshinobu Arai; Kuniki Kino; Kousaku Ohinata |
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Publication Detail:
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Type: Journal Article Date: 2012-08-01 |
Journal Detail:
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Title: Molecular nutrition & food research Volume: 56 ISSN: 1613-4133 ISO Abbreviation: Mol Nutr Food Res Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101231818 Medline TA: Mol Nutr Food Res Country: Germany |
Other Details:
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Languages: eng Pagination: 1456-63 Citation Subset: IM |
Copyright Information:
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© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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