NBCe1 expression is required for normal renal ammonia metabolism.

NBCe1 expression is required for normal renal ammonia metabolism. Am J Physiol Renal Physiol. 2015 Jul 29;:ajprenal.00219.2015 Authors: Handlogten ME, Osis G, Lee HW, Romero MF, Verlander JW, Weiner ID Abstract The mechanisms regulating proximal tubule ammonia metabolism are incompletely understood. The current studies address the role of the proximal tubule basolateral, electrogenic, sodium-coupled bicarbonate cotransporter, NBCe1 (Slc14a4), in renal ammonia metabolism. We used mice with heterozygous and homozygous NBCe1 gene deletion, and compared these mice to their wild type littermates. Because homozygous NBCe1 gene deletion causes 100% mortality prior to day 25, we studied mice at day 8 (±1 day). Both heterozygous and homozygous gene deletion caused a gene dose-related decrease in serum bicarbonate. The ability to lower urinary pH was intact, and even accentuated, with NBCe1 deletion. However, in contrast to the well-known effect of metabolic acidosis to increase urinary ammonia excretion, NBCe1 deletion caused a gene dose-related decrease in ammonia excretion. There was no identifiable change in proximal tubule structure by light microscopy. Examination of proteins involved in renal ammonia metabolism showed decreased expression of phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK), key enzymes in proximal tubule ammonia generation, and increased expression of glutamine synthetase, which recyc...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research