Response of ammoniagenesis to acute alkalosis.

To examine the response of ammonia production to acute alkalosis, isolated rat kidneys were perfused with 5 mM glucose and 0.5 mM glutamine for an initial 45 min at pH 7.7, achieved by raising the perfusate HCO3 concentration or reducing the PCO2, followed by one or more 45-min periods at a normal pH. During the initial high pH period, respiratory alkalosis had no effect on NH3 production in comparison with perfusions at a normal pH. However, during the subsequent 45-min period at a normal pH, kidneys exposed initially to a high pH produced less NH3 than those perfused at a normal pH for the entire experiment. This suppression of ammoniagenesis abated during an additional 45 min of perfusion at a normal pH. Kidneys exposed to metabolic alkalosis produced more NH3 than controls during the initial 45 min of perfusion. However, similar to respiratory alkalosis, NH3 production was lower than controls during the subsequent 45 min of perfusion at a normal pH. Hence a high bicarbonate concentration can rapidly, but transiently, stimulate NH3 production by the isolated rat kidney. However, a high pH, whether produced by metabolic or respiratory manipulations, suppresses ammoniagenesis. This suppressive effect requires 45 min of exposure to an elevated pH to be manifest and at least 45 min of exposure to a normal pH for reversal. The delayed response to alkalosis contrasts strikingly with the immediate effects of acute acidosis on NH3 production by the perfused kidney and suggests that different mechanisms account for the regulation of ammoniagenesis in response to acute decrements and elevations in pH.