title: Inducible nitric oxide regulates intestinal glutamine assimilation during chronic intestinal inflammation.
abstract: To facilitate assimilation of glutamine, different Na-dependent glutamine absorptive pathways are present in the rabbit small intestine, specifically B0AT1 in villus and SN2 in crypt cell brush border membrane. Further, both are uniquely regulated in the chronically inflamed intestine. B0AT1 is inhibited secondary to reduced number of brush border membrane (BBM) co-transporters while SN2 is stimulated secondary to an increased affinity for glutamine. These unique changes are reversible by treatment with a broad spectrum immune modulator such as glucocorticoids. However, whether inducible nitric oxide (iNO), known to be elevated in the mucosa of the chronically inflamed intestine, may be responsible for these co-transporter alterations is not known. In the present study, treatment of chronically inflamed rabbits with L-NIL, a selective inhibitor of iNO synthase, reversed the inhibition of B0AT1 in villus and the stimulation of SN2 in crypt cells. At the level of the co-transporter in the brush border membrane, inhibition of iNO production reversed the inhibition of villus B0AT1 by restoring the co-transporter numbers while the stimulation of crypt SN2 was reversed back to normal by restoring its affinity for glutamine. Western blot analyses of BBM proteins also confirmed the kinetic studies. Thus, L-NIL treatment restores the uniquely altered Na-glutamine co-transporters in the enterocytes of chronically inflamed intestine. All these data indicate that iNO functions as an upstream immune modulator directly regulating glutamine assimilation during chronic intestinal inflammation.
authors.affiliation: Department of Clinical and Translational Sciences, Joan C Edwards School of Medicine, Marshall University, 1600 Medical Centre Drive, Huntington, WV 25701, United States.
authors.forename: Subha
authors.initials: S
authors.lastname: Arthur
authors.affiliation: Department of Clinical and Translational Sciences, Joan C Edwards School of Medicine, Marshall University, 1600 Medical Centre Drive, Huntington, WV 25701, United States. Electronic address: sundaramu@marshall.edu.
authors.forename: Uma
authors.initials: U
authors.lastname: Sundaram
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D005759:Gastroenteritis / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D007082:Ileum / Q000166:cytology*; D007249:Inflammation / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits
chemical_list: D005973:Glutamine; D009569:Nitric Oxide
keywords: B0AT1; Crypt cells; Glutamine; Inducible nitric oxide; Inflammatory bowel diseases; Na-nutrient co-transport; SN2; Villus cells