title: Neutral Na-amino acid cotransport is differentially regulated by glucocorticoids in the normal and chronically inflamed rabbit small intestine.
abstract: Neutral Na-amino acid cotransport by system ATB(0) [e.g., Na-alanine cotransport (NAcT)] is an important means of assimilation of amino acids in the intestine. NAcT is inhibited during chronic intestinal inflammation by an alteration in the affinity for the amino acid. How glucocorticoids, a standard of treatment for diseases characterized by chronic intestinal inflammation, may affect NAcT during chronic enteritis is not known. Thus we first demonstrated that methylprednisolone (MP) stimulated NAcT in the normal intestine. The mechanism of stimulation was secondary to an increase in cotransporter numbers without an alteration in the affinity for the amino acid. Treatment with MP reversed the reduction in NAcT in villus cells from the chronically inflamed intestine. MP also alleviated the decrease in Na-K-ATPase activity in villus cells during chronic enteritis. However, MP treatment reversed the NAcT inhibition in villus cell brush border membrane vesicles from the inflamed intestine, which suggested an effect of MP at the level of the cotransporter itself. Kinetic studies demonstrated that the reversal of NAcT inhibition by MP was secondary to restoration in the affinity for the amino acid without a change in the V(max). Unaltered steady-state mRNA and immunoreactive protein levels of NAcT also indicated that the number of cotransporters was unchanged after MP treatment in the chronically inflamed intestine. These results indicated that MP reversed NAcT inhibition in the chronically inflamed intestine by restoring the affinity of the transporter for the amino acid while it stimulated NAcT in the normal intestine by increasing the cotransporter numbers. Therefore, MP differentially regulates NAcT in the normal and chronically inflamed intestine.
authors.affiliation: Section of Digestive Diseases, Dept of Medicine, West Virginia Univ School of Medicine, Morgantown, WV 26506, USA. usundaram@hsc.wvu.edu
authors.forename: Uma
authors.initials: U
authors.lastname: Sundaram
authors.forename: Sheik
authors.initials: S
authors.lastname: Wisel
authors.forename: Steven
authors.initials: S
authors.lastname: Coon
mesh_terms: D000409:Alanine / Q000378:metabolism; D026962:Amino Acid Transport System ASC / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004751:Enteritis / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008775:Methylprednisolone / Q000494:pharmacology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism
chemical_list: D026962:Amino Acid Transport System ASC; D005938:Glucocorticoids; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D000409:Alanine; D008775:Methylprednisolone