ISSN:
1432-2013
Keywords:
Ammoniagenesis
;
γ-Glutamyltransferase
;
Glutamine utilization
;
Acivicin
;
Antiluminal and luminal sites
;
Paraminohippurate
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The·role of γ-glutamyltransferase (γ-GT) in renal ammoniagenesis and glutamine utilization was evaluated in the intact functioning rat kidney. Total NH 4 + released, as the sum of renal venous and urinary NH 4 + , was measured under conditions of chronic mebolic acidosis and paraminohippurate infusion. Ammonia derived from extracellular γ-GT hydrolysis of glutamine was differentiated from that produced by intracellular phosphate dependent glutaminase (PDG) by employing acivicin, a γ-GT inhibitor. In nonacidotic animals acivicin administration inhibited γ-GT 95% and renal venous NH 4 + release 48%; NH 4 + release into the urine was not inhibited. Chronic metabolic acidosis elevated total NH 4 + release 2.5fold, associated with adaptive increase in both γ-GT and PDG; acivicin reduced total NH 4 + released 36% with both renal venous and urinary release effected. The contribution of γ-GT to total NH 4 + production doubles in metabolic acidosis in agreement with the adaptive rise in the in vitro assayed γ-GT activity. Luminal ammoniagenesis increases in chronic acidosis associated with a fall in urinary glutamine concentration and a rise in the blood to urine glutamine concentration gradient; γ-GT inhibition eliminates this gradient suggesting luminal ammoniagenesis is largely dependent upon the paracellular glutamine flux. In support of this, paraminohippurate (PAH) infusion increased total renal NH 4 + release due entirely to enhanced NH 4 + excretion. PAH stimulated luminal ammoniagenesis was associated with an acceleration of renal glutamine extraction and a steeper blood to urine glutamine diffusion gradient; acivicin blocked this response consistent with PAH secretion coupled to activation of intraluminal γ-GT and glutamine hydrolysis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00582380
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