Mechanism of inhibition of Na+-bile acid cotransport during chronic ileal inflammation in rabbits.
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 Na+-glucose cotransport was inhibited by a decrease in the cotransporter 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 chronically inflamed ileum. In villus cell brush-border membrane vesicles from the chronically inflamed ileum, Na+-bile acid cotransport was reduced as well, suggesting a direct effect at the cotransporter itself. Kinetic studies demonstrated 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 of inhibition of Na+-glucose, Na+-amino acid, and Na+-bile acid cotransport are different. These data suggest that different cotransporters are uniquely altered either secondary to their intrinsic differences or by different immune-inflammatory mediators during chronic ileitis.
Sundaram
U
U
Division of Digestive Diseases, Departments of Medicine and Physiology, Ohio State University School of Medicine, Columbus, Ohio 43210, USA.
Wisel
S
S
Stengelin
S
S
Kramer
W
W
Rajendran
V
V
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D006706:Homeostasis / Q000502:physiology; D007079:Ileitis / Q000378:metabolism* / Q000473:pathology; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D027981:Symporters
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C071908:sodium-bile acid cotransporter