Coulson R
J Biol Chem. 1976 Aug 25;251(16):4958-67.
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 mM. 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 14C-labeled cyclic nucleotides in the perfusate. During 60 min, 30% of added cyclic [14C]AMP was metabolized to renal [14C]adenine nucleotides (ATP, ADP, and AMP) and 30% to perfusate [14C]uric acid. Similarly, 20% of cyclic[14C]GMP was metabolized to renal [14C]guanine nucleotides (GTP, GDP, and GMP) and 30% to perfusate [14C]uric acid. Urine contained principally unchanged 14C-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 2- to 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 mumol of either 14C-labeled cyclic AMP or cyclic GMP was cleared from the plasma. Kidney cortex and liver were the principal tissues for 14C accumulation. Urinary excretion accounted for about 20 and 45% of the cyclic [14C]AMP and cyclic [14C]GMP lost from the plasma, respectively. The 14C found in the kidney and liver was present almost entirely as the respective purine mono-, di-, and trinucleotides. The other principal metabolite was [14C]allantoin, found in the urine and, to a lesser extent, the liver. The urine contained mostly unchanged 14C-labeled cyclic nucleotide. Unlike the findings with the perfused kidney, [14C]uric acid was not a significant metabolite of the 14C-labeled cyclic nucleotides in these in vivo experiments.
用含有初始浓度为0.1 mM的外源性3':5'-环磷酸腺苷（环磷腺苷）或3':5'-环磷酸鸟苷（环磷鸟苷）的循环介质灌注离体大鼠肾脏。两种环核苷酸都迅速从灌注液中清除。尿液排泄分别占灌注液中损失的环磷腺苷和环磷鸟苷的20%和40%左右。通过灌注液中14C标记的环核苷酸研究环核苷酸的代谢。在60分钟内，添加的环[14C]腺苷酸的30%代谢为肾脏[14C]腺嘌呤核苷酸（三磷酸腺苷、二磷酸腺苷和一磷酸腺苷），30%代谢为灌注液[14C]尿酸。同样，环[14C]鸟苷酸的20%代谢为肾脏[14C]鸟嘌呤核苷酸（三磷酸鸟苷、二磷酸鸟苷和一磷酸鸟苷），30%代谢为灌注液[14C]尿酸。尿液中主要含有未变化的14C标记的环核苷酸。向灌注液中添加0.1 mM环磷腺苷可使肾脏三磷酸腺苷和二磷酸腺苷含量升高2倍。向灌注液中添加0.1 mM的环磷腺苷或环磷鸟苷也可使肾脏尿酸生成量升高2至3倍。还在完整大鼠中研究了外源性环核苷酸代谢产物的生成和分布。注射后60分钟内，14C标记的环磷腺苷或环磷鸟苷中的3.3 μmol从血浆中清除。肾皮质和肝脏是14C积累的主要组织。尿液排泄分别占血浆中损失的环[14C]腺苷酸和环[14C]鸟苷酸的20%和45%左右。在肾脏和肝脏中发现的14C几乎完全以各自的嘌呤单核苷酸、二核苷酸和三核苷酸形式存在。另一种主要代谢产物是[14C]尿囊素，存在于尿液中，在肝脏中含量较少。尿液中大多含有未变化的14C标记的环核苷酸。与灌注肾脏的结果不同，在这些体内实验中，[14C]尿酸不是14C标记的环核苷酸的主要代谢产物。
