Mechanism of glucocorticoid-mediated reversal of inhibition of Cl(-)/HCO(-)(3) exchange during chronic ileitis.
In the normal ileum, coupled NaCl absorption occurs via the dual operation of Na(+)/H(+) and Cl(-)/HCO(-)(3) exchange on the brush-border membrane (BBM) of villus cells. In a rabbit model of chronic small intestinal inflammation we determined the cellular mechanism of inhibition of NaCl absorption and the effect of steroids on this inhibition. Cl(-)/HCO(-)(3) but not Na(+)/H(+) exchange was reduced in the BBM of villus cells during chronic ileitis. Cl(-)/HCO(-)(3) exchange was inhibited secondary to a decrease in the affinity for Cl(-) rather than an alteration in the maximal rate of uptake of Cl(-) (V(max)). Methylprednisolone (MP) stimulated Cl(-)/HCO(-)(3) exchange in the normal ileum by increasing the V(max) of Cl(-) uptake rather than altering affinity for Cl(-). MP reversed the inhibition of Cl(-)/HCO(-)(3) exchange in rabbits with chronic ileitis. However, MP alleviated the Cl(-)/HCO(-)(3) exchange inhibition by restoring the affinity for Cl(-) rather than altering the V(max) of Cl(-) uptake. These data suggest that glucocorticoids mediate the alleviation of Cl(-)/HCO(-)(3) exchange inhibition in chronically inflamed ileum by reversing the same mechanism that was responsible for inhibition of this transporter rather than exerting a direct effect on the transporter itself, as was the case in normal ileum.
Coon
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Division of Digestive Diseases, Departments of Medicine and Physiology, Ohio State University School of Medicine, Columbus, Ohio 43210, USA.
Sundaram
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D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters; D002908:Chronic Disease; D005938:Glucocorticoids / Q000494:pharmacology*; D007079:Ileitis / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D005938:Glucocorticoids; D017923:Sodium-Hydrogen Exchangers; D008775:Methylprednisolone