title: Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  A novel CCK-dependent vasorelaxing RF decreases both blood pressure and food intake.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kagebayashi
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Kontani
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mizushige
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Arai
authors.forename: Kuniki
authors.initials: K
authors.lastname: Kino
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002766:Cholecystokinin / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D004151:Dipeptides; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D011949:Receptors, Cholecystokinin; D014665:Vasodilator Agents; C048251:phenylalanylarginine; D009569:Nitric Oxide; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin