Intestinal absorption of stable cyclic dipeptides by the oligopeptide transporter in rat

• Published in: Journal of pharmacy and pharmacology Vol. 50; no. 2; p. 167
• Main Authors: Mizuma, T, Masubuchi, S, Awazu, S
• Format: Journal Article
• Language: English
• Published: England 01.02.1998
• Subjects: Animals; Biological Transport - drug effects; Carrier Proteins - metabolism; Dipeptides - chemistry; Dipeptides - pharmacokinetics; Drug Stability; Intestinal Absorption; Intestinal Mucosa - metabolism; Jejunum - metabolism; Male; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacokinetics; Rats; Rats, Wistar; Serous Membrane - metabolism; Structure-Activity Relationship
• ISSN: 0022-3573
• DOI: 10.1111/j.2042-7158.1998.tb06172.x

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.