Effect of cycloheximide on corticosteroid-induced changes in colonic function

Chronic parenteral mineralocorticoid and glucocorticoid treatment increases colonic sodium and water absorption and mucosal Na-K-ATPase activity. Cycloheximide, a protein synthesis inhibitor, was utilized to compare the mechanisms of action of these corticosteroids. Rats were injected with 50 or 100 μg/100 g body wt cycloheximide every 12 h, 0.5 or 3 mg/100 g deoxycorticosterone (DOCA) daily, or 3 mg/100 g methylprednisolone (MP) daily, singly or in combination for 2 days. In situ colonic perfusion was then performed. Net electrolyte and water absorption, transmural potential difference, and the specific activity of Na-K-ATPase were muasured. Cycloheximide alone did not alter colonic water, sodium, or chloride absorption or Na-K-ATPase activity but did increase transmural potential difference. DOCA-induced increases in colonic absorption and Na-K-ATPase were completely prevented by cycloheximide. Cycloheximide completely prevented the increase in Na-K-ATPase in MP-treated rats but only partially reduced the MP-induced increase in sodium and water absorption. These results suggest that this enzyme is not the primary site of glucocorticoid action. It remains to be determined whether an increase in Na-K-ATPase activity is a necessary part of the maximal colonic response to chronic glucocorticoid treatment.