Mechanism of inhibition of Na1-glucose cotransport in the chronically inflamed rabbit ileum

Sundaram, U., S. Wisel, V. M. Rajendren, and A. B. West. Mechanism of inhibition of Na1-glucose cotransport in the chronically inflamed rabbit ileum. Am. J. Physiol. 273 (Gastrointest. Liver Physiol. 36): G913–G919, 1997.—In a rabbit model of chronic ileal inflammation, we previously demonstrated that coupled NaCl absorption was reduced because of an inhibition of Cl/HCO3 2 but not Na1/H1 exchange on the brush-border membrane (BBM) of villus cells. In this study we determined the alterations in Na1-stimulated glucose [Na1-O-methyl-D-glucose (Na1-OMG)] absorption during chronic ileitis. Na1-OMG uptake was reduced in villus cells from the chronically inflamed ileum. Na1-K1adenosinetriphosphatase (ATPase), which provides the favorable Na1 gradient for this cotransporter in intact cells, was found to be reduced also. However, in villus cell BBM vesicles from the inflamed ileum Na1-OMG uptake was reduced as well, suggesting an effect at the level of the cotransporter itself. Kinetic studies demonstrated that Na1-OMG uptake in the inflamed ileum was inhibited by a decrease in the maximal rate of uptake for OMG without a change in the affinity. Analysis of steady-state mRNA and immunoreactive protein levels of this cotransporter demonstrates reduced expression. Thus Na1-glucose cotransport was inhibited in the chronically inflamed ileum, and the inhibition was secondary to a decrease in the number of cotransporters and not solely secondary to an inhibition of Na1-K1-ATPase or altered affinity for glucose.