Renal ammoniagenesis in kidney slices from rats undergoing glycerol-induced acute tubular necrosis

Abstract

Summary. Compared to control, kidney slices from rats undergoing glycerol-induced ATN produce less ammonia from glutamate, but show no difference when glutamine is substrate. However, gluconeogenesis from glutamine, like glutamate, is decreased in acute tubular necrosis (ATN). We conclude that renal ammoniagenesis is influenced by ATN. Glycerolinduced ATN causes a relative increase in glutamine deamidation and a decrease in glutamate deamination.In an early in vitro study 2, we reported decreased ammonia production by kidney slices from rats undergoing glycerolinduced acute tubular necrosis (ATN). In contrast, Westenfelder et al. 3, found depressed glucose reabsorption, PAH extraction, and bicarbonates reabsorption, but no decrease in ammonium excretion in their in vivo study concerning glycerol-induced ATN. What is the reason for discrepancy? To determine this, we performed expanded in vitro studies on ammoniagenesis by renal slices from rats undergoing glycerol ATN. Differently, we now found no significant changes in ammoniagenesis, but decreased gluconeogenesis was still present. The obvious difference between this and our previous investigation 2 was that glutamate was the ammonia precursor earlier, while glutamine was used in the present study.Methods. Male Sprague-Dawley rats, weighing 250-350 g, were dehydrated for 24 h; 18 rats received a s.c. injection of 50% (V/V) glycerol-isotonic saline (1 ml/100 g b.wt) and 21 received an equal volume of isotonic saline. The rats were sacrificed 24 h later after blood was withdrawn from the lower aorta. Serum urea nitrogen was measured by standard procedures 4. In vitro methodology and measurements of ammonia and glucose were as previously described 2'5. Glutamine 0.6 mm was substrate. Statistics were assessed by Student's t-test using group analysis.

Effects of ischemia-reperfusion injury on renal ammonia metabolism and the collecting duct

“…and is then reabsorbed by the thick ascending limb of the loop of Henle (20,31). We are unaware of studies reporting proximal tubule ammoniagenesis in response to ischemiareperfusion injury, but in another model of acute renal injury, glycerol-induced acute renal injury, renal ammoniagenesis is unchanged (48). Ischemia-reperfusion injury decreases Na ϩ /H ϩ exchanger-3 (NHE-3) and Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC-2) expression, the transporters involved in proximal tubule and thick ascending limb of the loop of Henle ammonia transport (17,34,66,67), suggesting ammonia transport may be decreased in these segments.…”