Mechanism of inhibition of Na1-bile acid cotransport during chronic ileal inflammation in rabbits

Sundaram, U., S. Wisel, S. Stengelin, W. Kramer, and V. Rajendran. Mechanism of inhibition of Na1-bile acid cotransport during chronic ileal inflammation in rabbits. Am. J. Physiol. 275 (Gastrointest. Liver Physiol. 38): G1259– G1265, 1998.—In the chronically inflamed ileum, unique mechanisms of alteration of similar transport processes suggest regulation by different immune-inflammatory mediator pathways. In a rabbit model of chronic ileitis, we previously demonstrated that Na1-glucose cotransport was inhibited by a decrease in the cotransporter numbers, whereas Na1-amino acid cotransport was inhibited by a decrease in the affinity for the amino acid. In this study, we demonstrated that Na1-bile acid cotransport was reduced in villus cells from the chronically inflamed ileum. In villus cell brush-border membrane vesicles from the chronically inflamed ileum, Na1-bile acid cotransport was reduced as well, suggesting a direct effect at the cotransporter itself. Kinetic studies demonstrated that Na1-bile acid cotransport was inhibited by both a decrease in the affinity as well as a decrease in the maximal rate of uptake of the bile acid. Analysis of steady-state mRNA and immunoreactive protein levels of the Na1-bile acid cotransporter also demonstrated some reduction during chronic ileitis. Thus, in the chronically inflamed ileum, the mechanisms of inhibition of Na1-glucose, Na1-amino acid, and Na1-bile acid cotransport are different. These data suggest that different cotransporters are uniquely altered either secondary to their intrinsic differences or by different immuneinflammatory mediators during chronic ileitis.