Peptide transporter 1 is responsible for intestinal uptake of the dipeptide glycylsarcosine: studies in everted jejunal rings from wild-type and Pept1 null mice.

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Ma K, Hu Y, Smith DE

Peptide transporter 1 is responsible for intestinal uptake of the dipeptide glycylsarcosine: studies in everted jejunal rings from wild-type and Pept1 null mice.

J Pharm Sci. 2011 Feb;100(2):767-74. doi: 10.1002/jps.22277. Epub 2010 Sep 22.

PubMed ID

20862774 [ View in PubMed

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Abstract

The purpose of this study was to determine the relative importance of peptide transporter 1 (PEPT1) in the uptake of peptides/mimetics from mouse small intestine, using glycylsarcosine (GlySar). After isolating jejunal tissue from wild-type and Pept1 null mice, 2 cm intestinal segments were everted and mounted on glass rods for tissue uptake studies. [(14)C]GlySar (4 muM) was studied as a function of time, temperature, sodium and pH, concentration, and potential inhibitors. Compared with wild-type animals, Pept1 null mice exhibited a 78% reduction in GlySar uptake at pH 6.0 at 37 degrees C. GlySar uptake showed pH dependence, with peak values between pH 6.0 and 6.5 in wild-type animals, whereas no such tendency was observed in Pept1 null mice. GlySar exhibited Michaelis-Menten uptake kinetics and a minor nonsaturable component in wild-type animals. In contrast, GlySar uptake occurred only by a nonsaturable process in Pept1 null mice. GlySar uptake was significantly inhibited by dipeptides, aminocephalosporins, angiotensin-converting enzyme inhibitors, and the antiviral prodrug valacyclovir; these inhibitors had little, if any, effect on the uptake of GlySar in Pept1 null mice. The findings demonstrate that PEPT1 plays a critical role in the uptake of GlySar in jejunum and suggest that PEPT1 is the major transporter responsible for the intestinal absorption of small peptides.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Lisinopril	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details