The role of renal
glutamine synthesis for the rapid decrease in renal ammoniagenesis occurring early in the recovery phase (24 h) of
metabolic acidosis was studied in rats.
L-Methionine-DL-sulfoximine (MSO), an irreversible inhibitor of
glutamine synthetase, depressed the renal
enzyme activity by 50% but did not impair the recovery from
acidosis. Since extrarenal
glutamine synthesis was decreased by this manoeuvre with lowering of blood
glutamine, an intravenous load of
L-glutamine sufficient to elevate blood concentration to 1 mM was superimposed on the MSO treatment. The
glutamine load did not increase the ammoniuria. Infusion of
glutamine alone to rats recovering from
metabolic acidosis for 12-24 h did not change their ammoniuria. In contrast,
glutamine administration together with HCl produced a marked ammoniuric response in rats recovering from
acidosis. Conversely, the administration of
bicarbonate to chronically acidotic rats acutely depressed renal
ammonia production. It is concluded that
glutamine synthetase activity is probably not required for recovery from
metabolic acidosis, and that the post-
acidosis alkaline rebound occurring in the rat may play a direct role in suppressing the ammoniagenic pathway either by drastic reduction in mitochondrial permeability for
glutamine or acute inhibition of intramitochondrial deamidation of this
amino acid.