AJP - Renal Physiology, Vol 262, Issue 6 1092-F1099, Copyright © 1992 by American Physiological Society
Role of nucleoside uptake in renal postischemic ATP synthesis
A. Van Waarde, M. J. Avison, G. Thulin, K. M. Gaudio, R. G. Shulman and N. J. Siegel
Department of Molecular Biophysics, Yale University School of Medicine, New Haven, Connecticut 06510.
The role of nucleoside uptake in the enhanced metabolic recovery seen with
postischemic ATP.MgCl2 was assessed by determining the effect of
S-(p-nitrobenzyl)-6-thioinosine (NBTI) on postischemic ATP recovery in rats
given normal saline (NS), ATP.MgCl2, or adenosine after 45 min of bilateral
renal ischemia. In NS-infused animals, postischemic administration of NBTI
(250 nmol) had no significant effect on the pattern of ATP recovery. In
animals given 50 mumol ATP.MgCl2, coinfusion of NBTI significantly reduced
the renal ATP content 2 h after reperfusion but blocked only one-half of
the enhancement in renal ATP content compared with animals given ATP.MgCl2
alone. In animals postischemically infused with [2,5,8-3H]ATP.MgCl2 (50
mumol) there was significant labeling of nucleotides, nucleosides, and
bases after 2 h of reperfusion. The specific activity of the adenosine pool
was consistent with significant label uptake in the form of adenosine.
Coinfusion of NBTI led to a significant reduction in label incorporation
into renal ATP and total adenine nucleotide pools. These data are
consistent with an important role for an NBTI-sensitive nucleoside uptake
mechanism in the enhanced metabolic and functional recovery observed in
ischemically injured kidney treated by postischemic infusion of ATP.MgCl2.
