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1 Division of Gastroenterology, Departments of Medicine and Physiology, Ohio State University School of Medicine, Columbus, Ohio 43210; 2 Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06320; and 3 Department of Pathology, University of Texas, Galveston, Texas 77555
In a rabbit model
of chronic ileal inflammation, we previously demonstrated that coupled
NaCl absorption was reduced because of an inhibition of
Cl
/
but not
Na+/H+
exchange on the brush-border membrane (BBM) of villus cells. In this
study we determined the alterations in
Na+-stimulated glucose
[Na+-O-methyl-D-glucose
(Na+-OMG)] absorption during
chronic ileitis. Na+-OMG uptake
was reduced in villus cells from the chronically inflamed ileum.
Na+-K+-adenosinetriphosphatase
(ATPase), which provides the favorable Na+ gradient for this
cotransporter in intact cells, was found to be reduced also. However,
in villus cell BBM vesicles from the inflamed ileum
Na+-OMG uptake was reduced as
well, suggesting an effect at the level of the cotransporter itself.
Kinetic studies demonstrated that Na+-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
Na+-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 Na+-K+-ATPase
or altered affinity for glucose.
glucose absorption; sodium absorption; electrolyte transport; chronic intestinal inflammation; sodium-glucose cotransport; sodium-potassium-adenosinetriphosphatase; inflammatory bowel disease
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