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Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells.

Recent studies have revealed that diverse compounds lacking peptide bonds, such as valacyclovir and delta-aminolevulinic acid (delta-ALA), can be recognized by H+-coupled peptide transporters (PEPT1 and PEPT2). In the present study, recognition and transport characteristics of nonpeptidic compounds by the basolateral peptide transporter, which is distinct from PEPTs, were compared with those by PEPT1 using the human intestinal Caco-2 cells. [14C]Glycylsarcosine uptake via PEPT1 was inhibited by all nonpeptidic compounds tested. Similarly, most nonpeptidic compounds showed an inhibitory effect on [14C]glycylsarcosine uptake by the basolateral peptide transporter, although some kinds of nonpeptidic compounds, such as valine methyl ester, did not. Direct measurements of valacyclovir and delta-ALA transport revealed that both compounds were able to be transported by the basolateral peptide transporter. Because delta-ALA has been used recently in vitro and in clinical studies as an endogenous photosensitizer for photodynamic therapy, the intestinal transport characteristics of delta-ALA were further examined. Inhibition studies and Eadie-Hofstee plot analysis suggested that delta-ALA transport across the brush-border and basolateral membranes of the intestine was mainly mediated by peptide transporters. In addition, the apical-to-basolateral transport of delta-ALA was greater than that of the opposite direction. These findings provide the first evidence that the intestinal basolateral peptide transporter can recognize and transport nonpeptidic compounds, and play a definitive role in the absorption of delta-ALA.