Unique mechanism of inhibition of Na+-amino acid cotransport during chronic ileal inflammation.
In the chronically inflamed ileum, unique mechanisms of alteration of transport processes suggest regulation by different immune-inflammatory mediator pathways. We previously demonstrated that Na+-glucose cotransport in the chronically inflamed ileum was inhibited by a decrease in cotransporter number without a change in glucose affinity. The aim of this study was to determine the alterations in Na+-amino acid cotransport in chronically inflamed ileum produced by coccidial infection in rabbits. [3H]alanine uptake was performed in cells and vesicles by rapid filtration. In villus cells from chronically inflamed ileum, Na+-K+-ATPase was reduced 50% and Na+-alanine cotransport was also reduced (5.8 +/- 1.2 in normal and 1.4 +/- 0.5 nmol/mg protein in inflamed; n = 6, P < 0.05). [3H]alanine uptake in brush-border membrane vesicles was reduced in chronically inflamed ileum (73.2 +/- 1.2 in normal and 21.5 +/- 3.2 pmol/mg protein in inflamed; n = 3, P < 0.05), suggesting a direct effect on the cotransporter itself. Na+-amino acid cotransport in chronically inflamed ileum was inhibited by a decrease in affinity without a change in the maximal rate of uptake, and unaltered steady-state mRNA levels also suggested that the number of cotransporters was unchanged. Thus the mechanisms of inhibition of Na+-amino acid cotransport and Na+-glucose cotransport in chronically inflamed ileum are different. These observations suggest that different immune-inflammatory mediators may regulate different transport pathways during chronic ileitis.
Division of Digestive Diseases, Departments of Medicine and Physiology, Ohio State University School of Medicine, Columbus, Ohio 43210, USA.
U
U
Sundaram
S
S
Wisel
J J
JJ
Fromkes
D000409:Alanine / Q000378:metabolism*; D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D003048:Coccidiosis / Q000378:metabolism*; D004539:Eimeria; D007077:Ileal Diseases / Q000378:metabolism* / Q000469:parasitology; D007082:Ileum; D007249:Inflammation / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000469:parasitology; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D027981:Symporters; D014158:Transcription, Genetic
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D012333:RNA, Messenger; D027981:Symporters; C052168:sodium-alanine cotransporter; D012964:Sodium; D000409:Alanine