Relation of ammonia excretion adaptation to glutaminase activity in acidotic, subtotal-nephrectomized rats

Abstract

The response of renal ammonia excretion to acidosis was examined in adult rats with reduced renal mass (SNX). Three days after surgical ablation of 70% of renal mass, the activity of renal phosphate-dependent glutaminase (PDG) in SNX rats was 7.7 ± 1.5 μmoles of ammonia/100 mg/protein/min or approximately 50% of the activity in normal rats, but enhanced ammonia excretion per unit weight was observed in SNX rats. The cause(s) of the reduction in the specific activity of PDG (as well as the increase in ammonia excretion) is unknown. The PDG decrease was not due to apparent tissue damage and appeared to be a specific change, as the activity of renal succinate dehydrogenase, another mitochondrial inner-membrane enzyme, did not decrease in SNX rats. Ammonia excretion showed no significant response to an acute acid load (ammonium chloride, 5 mmoles/kg of body wt) in SNX rats. Ammonia excretion, however, did adapt to repeated acid-loading (10 mmoles of ammonium chloride per kg of body wt per day for 3 days); ammonia excretion increased more than two-fold by the third day of treatment. This adaptive response was associated with a two-fold rise in renal PDG. Administration of actinomycin D, at a dose which produced no gross toxic signs (100 μg/kg/day i.p), inhibited virtually all the increases in both ammonia excretion and PDG activity.