POSTISCHEMIC ATP-MGCL2 PROVIDES PRECURSORS FOR THE RESYNTHESIS OF CELLULAR ATP

Abstract

Accelerated recovery of renal ATP levels have been documented in rats given a postischemic infusion of ATP-MgCl2. This observation could be related to a direct entry of ATP as a source of metabolic energy or to augmentation of the resynthesis of cellular ATP. To distinguish between these possibilities, rats were infused with either ATP-MgCl2 (25 μmoles), AMP-MgCl2 (25 μmoles) or normal saline (NS) after 45 min of renal ischemia. Renal cortical ATP levels were determined continuously in vivo, prior to, during and for 120 min after the ischemic injury using 31p NMR spectroscopy (TMR-32; 32.5 MHz for 31p). During the ischemia, cellular ATP levels fell rapidly and remained <10% of control values in all rats. ATP levels returned to 50% of control values within 10 min after the ischemic insult in all animals. In rats given NS, renal cortical levels of ATP recovered to only 65±2% at 2 hrs indicating a very slow and incomplete regeneration of cellular nucleotides. In contrast, the animals infused with ATP-MgCl2 (81±3%) or AMP-MgCl2 (83±4%) had significantly better (P<0.01) recovery of cellular ATP. Since ATP-MgCl2 and AMP-MgCl2 produced a similar result, it would appear that the infused ATP was not necessarily a direct source of cellular energy. Moreover, these findings would suggest that the postischemic infusion of ATP-MgCl2 provides precursors for the repletion of the tissue nucleotide pool and resynthesis of cellular ATP.