Mechanism of dipeptide stimulation of its own transport in a human intestinal cell line.
The initial objective of this study was to investigate whether the presence of dipeptide in the culture medium stimulates the uptake of dipeptide by a human intestinal cell line that expresses the oligopeptide transporter (Pept-1). The results showed that addition of glycylsarcosine (Gly-Sar) for 24 hr to the culture medium significantly increased the rate of glycylglutamine (Gly-Gln) uptake by Caco-2 cells. Furthermore, this stimulation in transport was also observed when Cefadroxil (beta-lactam antibiotic) instead of Gly-Gln was used as a probe but did not occur when Gly-Sar was added to the culture medium for only 2 hr or when Gly-Sar was substituted by a corresponding mixture of glycine plus sarcosine. The subsequent objective of the study was to investigate the mechanism of stimulation in transport described earlier. The results showed that the addition of Gly-Sar for 24 hr to the culture medium: (1) increased the Vmax of Gly-Gln transport by two-fold without affecting its Km, (2) increased the protein mass of Pept-1 by more than two-fold, (3) increased the abundance of Pept-1 mRNA by three-fold, and (4) had no effect on Gly-Gln transport when an inhibitor of trans-Golgi network (brefeldin) was added to the culture medium, but still increased the abundance of Pept-1 mRNA. In conclusion, the results show that dipeptides stimulate their own transport by increasing the membrane population of Pept-1. The molecular mechanism appears to be an increase in expression of the gene encoding Pept-1. A therapeutic application of the present results is that if bioavailability of orally administered peptidomimetic drugs is limited, patients may be tried on a high-protein diet to enhance their absorption.[1]References
- Mechanism of dipeptide stimulation of its own transport in a human intestinal cell line. Thamotharan, M., Bawani, S.Z., Zhou, X., Adibi, S.A. Proc. Assoc. Am. Physicians (1998) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
