Renal glutaminases: Diamox inhibition of glutamyltransferase

Ammonia (NH3) production by the rat kidney was studied after an acute administration of acetazolamide (Diamox). Diamox reduced renal ammonia release (renal vein NH3 + urine NH3 - arterial NH3) 60 PERCENT IN The intact functioning kidney. Ammonia production by whole-kidney homogenates was decreased by Diamox, confirming the drug's action as inhibiting glutaminase activity. Additional studies demonstrated the inhibited glutaminase was localized in the cytoplasm; the glutaminase activity of the mitochondrial fraction was unaffected by Diamox. Isolated perfused kidneys from Diamox-treated rats confirmed that the drug reduced ammonia production by inhibiting glutamyltransferase; in addition, inhibition was shown to be of a competitive nature. We therefore conclude that cytoplasmic glutamyltransferase is the major producer of ammonia in the nonacidotic rat kidney and that it is competitively inhibited by Diamox.