Inhibition of glutamine synthetase in the mouse kidney: a novel mechanism of adaptation to metabolic acidosis.

摘要: As part of a study on the regulation renal ammoniagenesis in mouse kidney, we investigated effect chronic metabolic acidosis glutamine synthesis by isolated proximal tubules. The results obtained reveal that, tubules from control mice, occurred at high rates glutamate and proline and, to lesser extent, ornithine, alanine, aspartate. A 48 h, caused marked inhibition near-physiological concentrations both alanine that were avidly metabolized tubules; also greatly stimulated utilization metabolism. These effects accompanied large increase (i) proline, gluconeogenesis (ii) ammonia accumulation glutamine. In cortex acidotic activity phosphoenolpyruvate carboxykinase increased 4-fold, but dehydrogenase did not change; contrast with what is known rat cortex, markedly diminished synthetase protein level, mRNA level cortex. strongly suggest an important regulatory component availability ammonium ions be excreted for defending systemic acid-base balance. Furthermore, they show rodents, species-specific.