The mechanism of the increase in renal ammoniagenesis in the rat with acute metabolic acidosis.

Chronic metabolic acidosis causes several biochemical changes in the rat kidney: perhaps the most prominent of these is the increase in ammonia production from glutamine and the increase in activity of phosphate-dependent glutaminase [ 11. The changes with acute acidosis are less clear and although there is an early increase in total renal production of ammonia [2] no enzymatic change has been described to explain this. Since changes in pH and bicarbonate alone could not be the stimulus for this renal metabolic adaptation, we looked for and demonstrated the presence of a factor in the plasma of acutely acidotic rats which stimulated glutamine uptake and ammoniagenesis by renal slices from normal rats [3]. We now describe a possible mechanism for this ammoniagenie response to acute acidosis in the rat. Our studies have focussed on the kidney since although the liver, brain and intestine metabolise glutamine, none of these organs show any enzymatic adaptation in response to metabolic acidosis.