title: Regulation of sodium-glutamine cotransport in villus and crypt cells by glucocorticoids during chronic enteritis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These data indicate that glucocorticoids function as an upstream broad spectrum immune modulator in the chronically inflamed intestine.
authors.affiliation: Section of Digestive Diseases and Clinical and Translational Science Institute West Virginia University Health Sciences Center, Morgantown, West Virginia 26506, USA.
authors.forename: Subha
authors.initials: S
authors.lastname: Arthur
authors.forename: Prosenjit
authors.initials: P
authors.lastname: Saha
authors.forename: Shanmuga
authors.initials: S
authors.lastname: Sundaram
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kekuda
authors.forename: Uma
authors.initials: U
authors.lastname: Sundaram
mesh_terms: D058739:Aberrant Crypt Foci / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D002908:Chronic Disease; D004751:Enteritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005973:Glutamine / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008871:Microvilli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D000893:Anti-Inflammatory Agents; D005973:Glutamine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D008775:Methylprednisolone