Mechanism of inhibition of proton: dipeptide co-transport during chronic enteritis in the mammalian small intestine.
Amino acids, a critical energy source for the intestinal epithelial cells, are more efficiently assimilated in the normal intestine via peptide co-transporters such as proton:dipeptide co-transport (such as PepT1). Active uptake of a non-hydrolyzable dipeptide (glycosarcosine) was used as a substrate and PepT1 was found to be present in normal villus, but not crypt cells. The mRNA for this transporter was also found in villus, but not crypt cells from the normal rabbit intestine. PepT1 was significantly reduced in villus cells also diminished in villus cell brush border membrane vesicles both from the chronically inflamed intestine. Kinetic studies demonstrated that the mechanism of inhibition of PepT1 during chronic enteritis was secondary to a decrease in the affinity of the co-transporter for the dipeptide without an alteration in the maximal rate of uptake (Vmax). Northern blot studies also demonstrated unaltered steady state mRNA levels of this transporter in the chronically inflamed intestine. Proton dipeptide transport is found in normal intestinal villus cells and is inhibited during chronic intestinal inflammation. The mechanism of inhibition is secondary to altered affinity of the co-transporter for the dipeptide.
Sundaram
Uma
U
Section of Digestive Diseases, Department of Medicine, West Virginia University School of Medicine, Medical Center Drive, Box 9161, Morgantown, WV 26506, USA. usundaram@hsc.wvu.edu
Wisel
Sheik
S
Coon
Steven
S
D000818:Animals; D001692:Biological Transport; D002908:Chronic Disease; D004151:Dipeptides / Q000378:metabolism*; D004751:Enteritis / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D000074011:Peptide Transporter 1; D011522:Protons; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011817:Rabbits; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D004151:Dipeptides; D000074011:Peptide Transporter 1; D011522:Protons; D012333:RNA, Messenger; D027981:Symporters