EFFECTS OF DEXAMETHASONE ON GLUTAMINE-METABOLISM IN THE ISOLATED VASCULARLY PERFUSED RAT SMALL-INTESTINE

Post-stress metabolism is associated with a large glutamine (Gln) efflux from muscle and an increased Gln utilization by the small intestine. Both appear to be modulated by corticosteroids. The present investigation was performed to better characterize the mechanism of corticoid action on Gln metabolism in an isolated preparation of vascularly perfused rat small intestine. In all perfusions, a synthetic perfusate free from blood components was used with only 0.6 mM Gln and 10 mM glucose as substrates. Irrespective of dexamethasone concentrations in the vascular perfusate (none, 0.25 mg l-1, or 2.5 mg l-1), isolated intestines from normal rats exhibited unchanged extraction rates of Gln (-85 +/- 8, -89 +/- 10, and -87 +/- 16 nmol min-1 g-1) and unchanged production rates of alanine (43 +/- 9, 40 +/- 7, and 51 +/- 5 nmol min-1 g-1) and ammonia (49 +/- 15, 45 +/- 13, and 54 +/- 13 nmol min-1 g-1). Similarly, when intestines were vascularly perfused 2 or 9 days after dexamethasone injection (0.45 mg kg-1 BW), net Gln uptake also remained unchanged (-88 +/- 16 and -84 +/- 11 nmol min-1 g-1). There was, however, a shift in nitrogenous products of Gln metabolism from ammonia (-31% and -38%) to alanine (+16% and +64%). Thus, the failure of dexamethasone to increase directly on the mucosa, dexamethasone could regulate intestinal Gln consumption in vivo by indirect mechanisms possibly involving extramucosal tissues. Dexamethasone pretreatment may modulate the pattern of nitrogenous products in portal venous blood presented to the liver and thus support enhanced nitrogen loss through ureagenesis by metabolic cooperation between gut and liver.