AJP - Renal Physiology, Vol 255, Issue 6 1122-F1127, Copyright © 1988 by American Physiological Society
Contribution of purine nucleotide cycle to intranephron ammoniagenesis in rats
K. Tamura and H. Endou
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
To evaluate the contribution of the purine nucleotide cycle (PNC) in renal
ammoniagenesis, ammonia production (AP) in cortical tubular suspensions and
microdissected nephron segments of control and acidotic rats was determined
using various amino acids, including glutamine (Gln) and aspartate (Asp).
In the cortical tubular suspensions, the best substrate for ammoniagenesis
was Gln (153.1 +/- 19.4 nmol.mg protein-1.15 min-1) followed by Asp (70.9
+/- 11.4). Metabolic acidosis resulted in a significant increase of AP only
from Gln (316.5 +/- 36.1 nmol.mg protein-1.15 min-1, P less than 0.01 vs.
control). Intranephron distribution of AP (pmol/mm or a glomerulus/15 min)
from Gln showed that the first segment of the proximal tubule (S1) was
highest in control (95.7 +/- 9.0), and its AP markedly increased in
acidosis (221.6 +/- 8.3, P less than 0.001 vs. control). The most
interesting and striking finding was that with Asp as a substrate, AP was
maximal in S1 (165.0 +/- 32.8), with a value exceeding that from Gln. An
adenylosuccinase inhibitor, 6-mercaptopurine (0.1 mM), significantly
inhibited AP from Asp in S1 and S3, and from Gln in S1. On the contrary, a
specific inhibitor of phosphoenolpyruvate carboxykinase,
3-mercaptopicolinate (0.1 mM), caused a significant decrease of AP from
Gln, but not from Asp, in S1. From these results it could be concluded that
AP via PNC can occur at high rates, especially in S1, only when Asp is
present at high concentrations.
