Effect of acute alterations in acid-base balance on rat renal glutaminase and phosphoenolpyruvate carboxykinase gene expression.

During chronic acidosis, the levels of the rat renal mRNAs that encode the mitochondrial glutaminase (GA) and cytosolic phosphoenolpyruvate carboxykinase (PCK) are increased 6-fold. Following acute recovery of chronic acidosis, the levels of the two mRNAs are rapidly and coordinately decreased, returning to normal within 13-17 h. In contrast, the increases in GA and PCK mRNAs during acute onset of acidosis occur with very different kinetics. The increase in PCK mRNA occurs rapidly and reaches a maximum within 7 h, whereas the GA mRNA is increased after a 4-7-h lag and then plateaus at 14-17 h. Treatment with dexamethasone or with cAMP analogs significantly increases the level of renal PCK mRNA but has no effect on the level of GA mRNA. Nuclear run-on experiments indicate that the acute induction of PCK mRNA is primarily due to an increased rate of transcription. However, transcription of GA mRNA is unaffected by acute acidosis. Therefore, the changes in the two mRNAs are temporally coordinated but occur through different mechanisms. Furthermore, the inductive effects of acidosis are not mediated solely through glucocorticoid or cAMP regulatory elements.