Regulation of sodium-glutamine cotransport in villus and crypt cells by glucocorticoids during chronic enteritis
Article first published online: 16 APR 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 11, pages 2149–2157, November 2012
How to Cite
Arthur, S., Saha, P., Sundaram, S., Kekuda, R. and Sundaram, U. (2012), Regulation of sodium-glutamine cotransport in villus and crypt cells by glucocorticoids during chronic enteritis. Inflamm Bowel Dis, 18: 2149–2157. doi: 10.1002/ibd.22924
- Issue published online: 15 OCT 2012
- Article first published online: 16 APR 2012
- Manuscript Accepted: 30 JAN 2012
- Manuscript Received: 1 DEC 2011
- National Institute of Diabetes and Digestive and Kidney Diseases Research. Grant Numbers: DK-45062, DK-58034
- inflammatory bowel disease;
- intestinal nutrient absorption;
- regulation of amino acid absorption;
- Na-dependent glutamine cotransporters;
Assimilation of the preferred nutrient of enterocytes is mediated primarily by sodium (Na)-dependent cotransport (NGct) in the intestine. The predominant NGcT in villus cells, B0AT1, is inhibited secondary to a decrease in cotransporter numbers during chronic intestinal inflammation. In contrast, NGcT mediated by SN2 in crypt cells is stimulated secondary to increased affinity of the cotransporter for glutamine during chronic ileitis. Glucocorticoid is a mainstay of treatment for inflammatory bowel disease. However, its effect on NGcT is not known.
The inhibition of B0AT1 in villus cells during chronic intestinal inflammation was reversed back to normal by methylprednisolone (MP). This was secondary to the restoration of the cotransporter numbers in the brush border membrane rather than an alteration in the affinity. The stimulation of NGcT in crypt cells during chronic ileitis was also restored back to its normal levels by MP treatment. This reversal was secondary to the restoration of the altered affinity of the cotransporter SN2 for glutamine.
Kinetic studies and western blot analysis were consistent with functional studies for both cotransporters. Thus, glucocorticoids restore two uniquely altered Na-glutamine cotransporters, B0AT1 in villus and SN2 in crypt cells during chronic enteritis.
These data indicate that glucocorticoids function as an upstream broad spectrum immune modulator in the chronically inflamed intestine. (Inflamm Bowel Dis 2012;)