title: Intestinal absorption of stable cyclic dipeptides by the oligopeptide transporter in rat.
abstract: Intestinal absorption of four cyclic dipeptides was studied in the everted small intestine of the rat. Cyclic seryltyrosine (cyclo(Ser-Tyr)) was stable enough to be transported whereas linear seryltyrosine was not. The absorption clearance of cyclo(Ser-Tyr) was concentration-dependent, and for cyclo(Ser-Tyr) at 125 microM decreased in the presence of glycylsarcosine (10 mM) or cephalexin (10 mM), which were reported to be absorbed by oligopeptide transporter. The absorption clearance was also reduced at 4 degrees C and in the presence of 1 mM dinitrophenol. Kinetic analysis of cyclo(Ser-Tyr) absorption showed that Km and Vmax were 19.8 microM and 0.295 nmol min(-1) cm(-1), respectively. It was also suggested that cyclic aspartylphenylalanine and cyclic histidylphenylalanine were absorbed by oligopeptide transporters, but cyclic histidylproline was not. The absorption clearance of cyclo(Ser-Tyr) in the control was much higher than the value of the correlation line representing a plot of passive transport (which was obtained from the absorption clearance of cyclic peptides in the presence of glycylsarcosine (10 mM)) against hydrophobicity (oil-water partition coefficient). These results indicate that cyclo(Ser-Tyr) is absorbed by the oligopeptide transporter.
authors.affiliation: Department of Biopharmaceutics and Drug Rational Research Center, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizuma
authors.forename: S
authors.initials: S
authors.lastname: Masubuchi
authors.forename: S
authors.initials: S
authors.lastname: Awazu
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010456:Peptides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012704:Serous Membrane / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D004151:Dipeptides; D010456:Peptides, Cyclic