The apical H⁺-coupled peptide transporter (PEPT1) and basolateral peptide transporter in human intestinal Caco-2 cells were functionally compared by the characterization of [¹⁴C]glycylsarcosine transport. The glycylsarcosine uptake via the basolateral peptide transporter was less sensitive to medium pH than uptake via PEPT1 and was not transported against the concentration gradient. Kinetic analysis indicated that glycylsarcosine uptake across the basolateral membranes was apparently mediated by a single peptide transporter. Small peptides and -lactam antibiotics inhibited glycylsarcosine uptake by the basolateral peptide transporter, and these inhibitions were revealed to be competitive. Comparison of the inhibition constant values of various -lactam antibiotics between PEPT1 and the basolateral peptide transporter suggested that the former had a higher affinity than the latter. A histidine residue modifier, diethyl pyrocarbonate, inhibited glycylsarcosine uptake by both transporters, although the inhibitory effect was greater on PEPT1. These findings suggest that a single facilitative peptide transporter is expressed at the basolateral membranes of Caco-2 cells and that PEPT1 and the basolateral peptide transporter cooperate in the efficient transepithelial transport of small peptides and peptidelike drugs.

intestinal absorption; -lactam antibiotics; human intestinal Caco-2 cells

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