Basic Information
ID: ALA2073870
Journal: Pharm Res
Title: Inhibitory effect of zinc on PEPT1-mediated transport of glycylsarcosine and beta-lactam antibiotics in human intestinal cell line Caco-2.
Authors: Okamura M, Terada T, Katsura T, Saito H, Inui K.
Abstract: The aim of this study was to examine the effects of zinc on the intestinal peptide transporters (PEPT1 and basolateral peptide transporter) and to elucidate the mechanism of the interactions.Caco-2 cells were pretreated with zinc, and the uptake studies were carried out.Zinc treatment resulted in the inhibition of [14C]glycylsarcosine (Gly-Sar) uptake via PEPT1 in a concentration-dependent manner, whereas it showed moderate inhibitory effect on the basolateral peptide transporter. Zinc also inhibited the uptake of oral beta-lactam antibiotics such as ceftibuten and cephradine by PEPT1. Kinetic analysis showed that zinc treatment increased Km values without affecting Vmax values of the [14C]Gly-Sar uptake. The inhibition of [14C]Gly-Sar uptake induced by zinc was observed in the presence of an H+ gradient but not in the absence of an H+ gradient.These results indicate that zinc is a competitive inhibitor of PEPT1. Zinc inhibited the PEPT1 function, possibly by interacting with histidine residues of PEPT1 that are part of an H+-binding site. These findings would provide important information for clinical, physiologic, and biochemical aspects of peptide transporters.
CiteXplore: 14567632
Patent ID: ┄
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