Intestinal absorption of stable cyclic dipeptides by the oligopeptide transporter in rat.
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.
Mizuma
T
T
Department of Biopharmaceutics and Drug Rational Research Center, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Masubuchi
S
S
Awazu
S
S
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
D002352:Carrier Proteins; D004151:Dipeptides; D010456:Peptides, Cyclic