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

In the chronically inflamed ileum, unique mechanisms of alteration of simil ar transport processes suggest regulation by different immune-inflammatory mediator pathways. In a rabbit model of chronic ileitis, we previously demo nstrated that Na+-glucose cotransport was inhibited by a decrease in the co transporter numbers, whereas Na+-amino acid cotransport was inhibited by a decrease in the affinity for the amino acid. In this study, we demonstrated that Na+-bile acid cotransport was reduced in villus cells from the chroni cally inflamed ileum. In villus cell brush-border membrane vesicles from th e chronically inflamed ileum, Na+-bile acid cotransport was reduced as well , suggesting a direct effect at the cotransporter itself. Kinetic studies d emonstrated that Na+-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 Na+-bile acid cotransporter also demonstrated some reduction during chronic ileitis. Thus, in the chronically inflamed ileum, the mechanisms o f inhibition of Na+-glucose, Na+-amino acid, and Na+-bile acid cotransport are different. These data suggest that different cotransporters are uniquel y altered either secondary to their intrinsic differences or by different i mmune-inflammatory mediators during chronic ileitis.