M. Thamotharan et al., MECHANISM OF DIPEPTIDE STIMULATION OF ITS OWN TRANSPORT IN A HUMAN INTESTINAL-CELL LINE, Proceedings of the Association of American Physicians, 110(4), 1998, pp. 361-368
Citations number
16
Categorie Soggetti
Medicine, General & Internal","Medicine, Research & Experimental
The initial objective of this study was to investigate whether the pre
sence of dipeptide in the culture medium stimulates the uptake of dipe
ptide by a human intestinal cell line that expresses the oligopeptide
transporter (Pept-1). The results showed that addition of glycylsarcos
ine (Gly-Sar) for 24 hr to the culture medium significantly increased
the rate of glycylglutamine (Gly-Gln) uptake by Caco-2 cells. Furtherm
ore, this stimulation in transport was also observed when Cefadroxil (
beta-lactarn antibiotic) instead of Gly-Gln was used as a probe but di
d 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 investig
ate the mechanism of stimulation in transport described earlier. The r
esults showed that the addition of Gly-Sar for 24 hr to the culture me
dium: (1) increased the V-max of Gly-Gln transport by two-fold without
affecting its K-m, (2) increased the protein mass of Pept-1 by more t
han 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 tran
s-Golgi network (brefeldin) was added to the culture medium, but still
increased the abundance of Pept-1 mRNA. In conclusion, the results. s
how that dipeptides stimulate their own transport by increasing the me
mbrane population of Pept-1. The molecular mechanism appears to be an
increase in expression of the gene encoding Pept-1. A therapeutic appl
ication of the present results is that if bioavailability of orally ad
ministered peptidomimetic drugs is limited, patients may be tried on a
high protein diet to enhance their absorption.