Metabolism and Excretion of Exogenous Adenosine 3’S’-Monophosphate and Guanosine 3’S’-Monophosphate STUDIES IN THE ISOLATED PERFUSED RAT KIDNEY AND IN THE INTACT RAT*

Isolated rat kidneys were perfused with a recirculating medium containing exogenous adenosine 3’:5’-monophosphate (cyclic AMP) or guanosine 3’:5’-monophosphate (cyclic GMP) at an initial concentration of 0.1 IIIM. Both cyclic nucleotides were rapidly removed from the perfusate. Urinary excretion accounted for about 20% and 40% of the respective cyclic AMP and cyclic GMP lost from the perfusate. The metabolism of the cyclic nucleotides was studied by including ‘C-labeled cyclic nucleotides in the perfusate. During 60 min, 30% of added cyclic [l’C]AMP was metabolized to renal [“Cladenine nucleotides (ATP, ADP, and AMP) and 30% to perfusate [“C]uric acid. Similarly, 20% of cyclic[“C]GMP was metabolized to renal [14C ]guanine nucleotides (GTP, GDP, and GMP) and 30% to perfusate [“C]uric acid. Urine contained principally unchanged “C-labeled cyclic nucleotide. Addition of 0.1 mM cyclic AMP to the perfusate elevated the renal ATP and ADP contents 2-fold. Addition of 0.1 mM of either cyclic AMP or cyclic GMP to the perfusate also elevated the renal production of uric acid 2to 3-fold. The production and distribution of metabolites of exogenous cyclic nucleotides were also studied in the intact rat. Within 60 min after injection, 3.3 pmol of either ‘C-labeled cyclic AMP or cyclic GMP was cleared from the plasma. Kidney cortex and liver were the principal tissues for “C accumulation. Urinary excretion accounted for about 20 and 45% of the cyclic [l*C]AMP and cyclic [l’C]GMP lost from the plasma, respectively. The “C found in the kidney and liver was present almost entirely as the respective purine mono-, di-, and trinucleotides. The other principal metabolite was [“C lallantoin, found in the urine and, to a lesser extent, the liver. The urine contained mostly unchanged “C-labeled cyclic nucleotide. Unlike the findings with the perfused kidney, [“Cluric acid was not a significant metabolite of the “C-labeled cyclic nucleotides in these in uiuo experiments.