UNIQUE MECHANISM OF INHIBITION OF NA-ACID COTRANSPORT DURING CHRONIC ILEAL INFLAMMATION( AMINO)

In the chronically inflamed ileum, unique mechanisms of alteration of transport processes suggest regulation by different immune-inflammator y mediator pathways. We previously demonstrated that Na+-glucose cotra nsport in the chronically inflamed ileum was inhibited by a decrease i n cotransporter number without a change in glucose affinity. The aim o f this study was to determine the alterations in Na+-amino acid cotran sport in chronically inflamed ileum produced by coccidial infection in rabbits. [H-3]alanine uptake was performed in cells and Vesicles by r apid 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). [H-3]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), suggestin g a direct effect on the cotransporter itself. Na+-amino acid cotransp ort in chronically inflamed ileum was inhibited by a decrease in affin ity without a change in the maximal rate of uptake, and unaltered stea dy-state mRNA levels also suggested that the number of cotransporters was unchanged. Thus the mechanisms of inhibition of Na+-amino acid cot ransport and Na+-glucose cotransport in chronically inflamed ileum are different. These observations suggest that different immune-inflammat ory mediators may regulate different transport pathways during chronic ileitis.