AJP - Renal Physiology, Vol 251, Issue 5 919-F932, Copyright © 1986 by American Physiological Society
ATP turnover and renal response of dog tubules to pH changes in vitro
C. Manillier, P. Vinay, L. Lalonde and A. Gougoux
In vivo the dog kidney responds to metabolic or respiratory acidosis by a
marked increment of its ammonia production (expressed per 100 milliliters
glomerular filtration rate). This phenomenon is related to a switch from
metabolic utilization of nonammoniagenic (lactate) to ammoniagenic
(glutamine) substrates to support ATP turnover in the proximal tubules. We
have proposed that in vivo the maximum activity of the ammoniagenic process
is fixed by the ATP turnover in this segment of the nephron. The maximal
glutamine metabolism is reached when 100% of this turnover is supported by
glutamine metabolism. We have studied how these concepts apply to the
adaptation of glutamine metabolism and ammonia production to a low pH in
vitro using proximal tubules of dogs incubated when one (lactate or
glutamine) or several (glutamine plus lactate or plus palmitate) substrates
are provided. At pH 7.4 glutamine alone supports already 71-76% of the
tissue ATP turnover (minimal and maximal values). With acidification this
fraction rises to nearly 87-94%, but this increases only modestly the
ammonia production. Reducing the ATP turnover with ouabain at pH 7.4
decreases the absolute glutamine utilization, which now supports only
45-50% of the ATP turnover. Again acidification increases this fraction to
90-99%. Addition of lactate with glutamine displaces part of the glutamine
metabolized, but greatly stimulates the synthesis of alanine. Fatty acids
depress ammonia production and blunt the tissue response to acidification.
Gluconeogenesis from lactate is minimally influenced by incubation pH. It
is concluded that the ATP turnover limits the metabolism of glutamine by
proximal tubules in vitro as in vivo in the dog, and that the response to
acidification is small in vitro because of the absence of alternative
substrates.
