AJP - Renal Physiology, Vol 250, Issue 4 720-F733, Copyright © 1986 by American Physiological Society
Increases of cell ATP produced by exogenous adenine nucleotides in isolated rabbit kidney tubules
J. M. Weinberg and H. D. Humes
The effects of exogenous nucleotides on adenine nucleotide metabolism and
cell cation levels in normal and O2-deprived isolated rabbit kidney tubules
were studied to gain insight into ways in which exogenous nucleotides could
contribute to ameliorating O2 deprivation-induced injury. In control
oxygenated tubules, 250 microM exogenous ATP, ADP, or AMP resulted in two-
to threefold increases of cell ATP over 75-90 min of incubation and smaller
relative increases of ADP and AMP. GTP was not increased. Exogenous
adenosine, inosine, and hypoxanthine were substantially less effective at
increasing intracellular nucleotides than equimolar concentrations of
exogenous nucleotides. Nucleotide-treated cells had higher levels of Ca2+
and Mg2+ than untreated cells. Treatment of O2-deprived tubules with
exogenous Mg-ATP improved recovery of ATP levels following O2 deprivation,
and tubules with mild injury increased their ATP levels to supranormal
values such as those seen in control oxygenated tubules treated with
nucleotides. Increases of tubule cell ATP levels required ongoing oxidative
metabolism and thus were not evident until the reoxygenation recovery
period. Exogenous ATP produced some improvement of other injury-associated
metabolic parameters but did not substantially alter the overall pattern of
tubule susceptibility to lethal cell injury. Allopurinol did not affect the
behavior of oxygenated or O2-deprived tubules irrespective of the presence
of exogenous ATP. These data clarify the potential for manipulating
intracellular ATP levels with exogenous nucleotides and the functional
consequences of such manipulation in oxygenated and O2-deprived renal
tubule cells.
