Unique mechanism of inhibition of Na1-amino acid cotransport during chronic ileal inflammation

Sundaram, U., S. Wisel, and J. J. Fromkes. Unique mechanism of inhibition of Na1-amino acid cotransport during chronic ileal inflammation. Am. J. Physiol. 275 (Gastrointest. Liver Physiol. 38): G483–G489, 1998.—In the chronically inflamed ileum, unique mechanisms of alteration of transport processes suggest regulation by different immuneinflammatory mediator pathways. We previously demonstrated that Na1-glucose cotransport in the chronically inflamed ileum was inhibited by a decrease in cotransporter number without a change in glucose affinity. The aim of this study was to determine the alterations in Na1-amino acid cotransport in chronically inflamed ileum produced by coccidial infection in rabbits. [3H]alanine uptake was performed in cells and vesicles by rapid filtration. In villus cells from chronically inflamed ileum, Na1-K1-ATPase was reduced 50% and Na1-alanine cotransport was also reduced (5.8 6 1.2 in normal and 1.4 6 0.5 nmol/mg protein in inflamed; n 5 6, P , 0.05). [3H]alanine uptake in brush-border membrane vesicles was reduced in chronically inflamed ileum (73.2 6 1.2 in normal and 21.5 6 3.2 pmol/mg protein in inflamed; n 5 3, P , 0.05), suggesting a direct effect on the cotransporter itself. Na1-amino acid cotransport in chronically inflamed ileum was inhibited by a decrease in affinity without a change in the maximal rate of uptake, and unaltered steady-state mRNA levels also suggested that the number of cotransporters was unchanged. Thus the mechanisms of inhibition of Na1-amino acid cotransport and Na1-glucose cotransport in chronically inflamed ileum are different. These observations suggest that different immune-inflammatory mediators may regulate different transport pathways during chronic ileitis.