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Abstract
In view of recent reports suggesting that acetazolamide (ACZ) inhibits renal ammoniagenesis
and the pentose phosphate pathway, its effects on renal metabolism were investigated
with rat isolated perfused kidney and isolated cortical tubules. In the isolated kidney
perfused with glutamine (2 mM) and glucose (5mM), ACZ (0.1 mM) resulted in a natriuresis
and bicarbonate diuresis and decreased NH3 production from 1.72 to 1.35 μmol/min/gm dry weight (p < 0.05). NH3 production was unchanged in control perfusions in which no inhibitor was added. With
kidneys from acidotic animals perfused with glutamine (2 mM) without glucose, NH3 production was unaltered by ACZ but glucose production decreased from 0.93 to 0.20
μmol/min/gm (p < 0.01). ACZ inhibited NH3 (14.2 to 12.6 μmol/min/gm, p < 0.01) and glucose (1.6 to 1.2 μmol/min/gm, p < 0.05)
and stimulated glutamate (2.2 to 2.9 μmol/min/gm, p < 0.01) production by isolated
tubules from normal rats incubated with 2 mM glutamine and had similar effects with
acidotic animals. Glucose production from malate was also inhibited. The increase
in glutamate and decrease in glucose production from glutamine, as well as malate,
suggest that ACZ inhibits ammoniagenesis by altering metabolism of the glutamine carbon
skeleton rather than by affecting glutamyl transferase. Finally, these results emphasize
that ACZ has definite effects on renal metabolism, which must be considered in interpreting
studies using it to elucidate hydrogen ion transport.
Abbreviations:
glomerular filtration rate ((GFR))To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
June 7,
1983
Received:
January 27,
1983
Footnotes
☆These studies were supported by P.H.S. Grant AM25248.
Identification
Copyright
© 1983 Published by Elsevier Inc.