POSTISCHEMIC THYROXINE STIMULATES RENAL MITOCHONDRIAL ADENINE-NUCLEOTIDE TRANSLOCATOR ACTIVITY

Postischemic thyroxin (T-4) enhances restitution of cellular ATP and a ccelerates recovery of renal function. This effect is not related to g lobal improvement in cell integrity. To determine the mechanism by whi ch recovery of cellular ATP is enhanced, the effect of T-4 On mitochon drial ATP production was evaluated using specific inhibitor stop assay s for mitochondrial phosphate transport and ADP translocator activity. Rats were subjected to 45-min renal ischemia and given normal saline (NS, 0.5 ml) or T-4 (20 mu g/kg) during the reflow period. By 30-min r eflow, the values for apparent endpoint of phosphate transport (PiTm, nmol P-i/mg mitochondrial protein) had recovered to rates seen in noni schemic animals (10.3 +/- 0.9) and remained stable at 120 min. T-4 tre atment did not affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min (6.7 +/- 0.5) and 120-min (13.7 +/- 1.0 ) reflow compared with nonischemic control rats (24.7 +/- 2.4). T-4 si gnificantly improved ADPTm by 30 min (10.1 +/- 0.6, P < 0.05). By 120 min T-4 stimulated ADPTm (37.7 +/- 5.2, P < 0.05) to exceed nonischemi c control values. These data suggest the following: 1) postischemic mi tochondrial PiTm recovers to control values by 30 min of reflow; 2) T- 4 does not augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial ADPTm; 4)postischemic T-4 significantly enhances mito chondrial nucleotide transport at 30-min reflow; 5) by 120-min reflow, T-4 rats have ADPTm which exceeds control values. These findings prov ide an understanding of at least one of the metabolic components that contribute to the enhanced recovery of cellular ATP resulting from pos tischemic T-4 administration.