Mechanism of inhibition of Na+-glucose cotransport in the chronically inflamed rabbit ileum.
In a rabbit model of chronic ileal inflammation, we previously demonstrated that coupled NaCl absorption was reduced because of an inhibition of Cl-/HCO3- 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.
Sundaram
U
U
Department of Medicine, Ohio State University School of Medicine, Columbus 43210, USA.
Wisel
S
S
Rajendren
V M
VM
West
A B
AB
D000818:Animals; D003048:Coccidiosis / Q000473:pathology / Q000503:physiopathology*; D004539:Eimeria; D007079:Ileitis / Q000469:parasitology / Q000503:physiopathology*; D007082:Ileum; D007249:Inflammation; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008757:Methylglucosides / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014158:Transcription, Genetic
D008562:Membrane Glycoproteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D051269:Sodium-Glucose Transporter 1; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase