| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Pharmaceutics, Royal Danish School of Pharmacy; and 2 Department of Zoophysiology, August Krogh Institute, DK-2100 Copenhagen, Denmark
The human intestinal
cell line Caco-2 was used as a model system to study the effects of
epidermal growth factor (EGF) on peptide transport. EGF decreased
apical-to-basolateral fluxes of [14C]glycylsarcosine
([14C]Gly-Sar) up to 50.2 ± 3.6%
(n = 6) of control values. Kinetic analysis of the
fluxes showed that maximal flux (Vmax) of
transepithelial transport decreased from 3.00 ± 0.17 nmol · cm
2 · min1 in
control cells to 0.50 ± 0.07 nmol · cm2 · min1 in cells
treated with 5 ng/ml EGF (n = 6, P < 0.01). The apparent Michaelis-Menten constant
(Km) was 2.71 ± 0.31 mM (n = 6) in control cells and 1.89 ± 0.28 mM (n = 6, not significantly different from control) in EGF-treated cells.
Similarly, apical uptake of [14C]Gly-Sar decreased in
cells treated with EGF, with an ED50 value of 0.36 ± 0.06 ng/ml (n = 6) EGF and a maximal inhibition of
80 ± 0.02% (n = 6). Vmax
decreased from 2.61 ± 0.4 to 1.06 ± 0.1 nmol · cm2 · min1
(n = 3, P < 0.05), whereas
Km remained constant. Basolateral Gly-Sar uptake
showed no changes in Vmax or
Km after EGF treatment (n = 3).
RT-PCR showed a decrease in hPepT1 mRNA (using glucose-6-phosphate dehydrogenase mRNA as control) in cells treated with EGF. Western blotting indicated a decrease in hPepT1 protein in cell lysates. We
conclude that EGF treatment decreases Gly-Sar transport in Caco-2 cells
by decreasing the number of peptide transporter molecules in the apical membrane.
intestinal oligopeptide transporter; growth factor; immunocytochemistry; laser scanning confocal microscopy
This article has been cited by other articles:
|
|
 |
|
  P. Hindlet, A. Bado, R. Farinotti, and M. Buyse Long-Term Effect of Leptin on H+-Coupled Peptide Cotransporter 1 Activity and Expression in Vivo: Evidence in Leptin-Deficient Mice J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 192 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shimakura, T. Terada, H. Saito, T. Katsura, and K.-i. Inui Induction of intestinal peptide transporter 1 expression during fasting is mediated via peroxisome proliferator-activated receptor {alpha} Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G851 - G856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Y. Lee, S. H. Park, Y. J. Lee, J. S. Heo, J. H. Lee, and H. J. Han EGF-induced inhibition of glucose transport is mediated by PKC and MAPK signal pathways in primary cultured chicken hepatocytes Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G744 - G750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shimakura, T. Terada, T. Katsura, and K.-I. Inui Characterization of the human peptide transporter PEPT1 promoter: Sp1 functions as a basal transcriptional regulator of human PEPT1 Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G471 - G477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Chanteux, F. Van Bambeke, M.-P. Mingeot-Leclercq, and P. M. Tulkens Accumulation and Oriented Transport of Ampicillin in Caco-2 Cells from Its Pivaloyloxymethylester Prodrug, Pivampicillin Antimicrob. Agents Chemother., April 1, 2005; 49(4): 1279 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimizu, S. Masuda, K. Nishihara, L. Ji, M. Okuda, and K.-i. Inui Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G664 - G670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Bravo, C. U. Nielsen, J. Amstrup, S. Frokjaer, and B. Brodin Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2 Am J Physiol Renal Physiol, February 1, 2004; 286(2): F385 - F393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Adibi Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G779 - G788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Daniel and I. Rubio-Aliaga An update on renal peptide transporters Am J Physiol Renal Physiol, May 1, 2003; 284(5): F885 - F892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Pan, T. Terada, M. Irie, H. Saito, and K.-I. Inui Diurnal rhythm of H+-peptide cotransporter in rat small intestine Am J Physiol Gastrointest Liver Physiol, July 1, 2002; 283(1): G57 - G64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ashida, T. Katsura, H. Motohashi, H. Saito, and K.-I. Inui Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells Am J Physiol Gastrointest Liver Physiol, April 1, 2002; 282(4): G617 - G623. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
