Inversely related oscillations in the contents of cyclic GMP and the total adenine nucleotides in steady‐state perfused rat hearts
Inversely related oscillations in the contents of cyclic GMP and the total adenine nucleotides in steady‐state perfused rat hearts
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稳态灌注大鼠心脏中环鸟苷酸含量和总腺嘌呤核苷酸的负相关振荡
DOI：
10.1016/0014-5793(81)80886-1
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发表时间：
1981
期刊：
影响因子：
3.5
通讯作者：
D. Perrett
中科院分区：
文献类型：
--
作者：
J. Mowbray;D. J. Bates;D. Perrett
在研究Langendorf灌注心脏中氨基酸与蛋白质的结合时，我们令人惊讶地观察到，当在2小时灌注期间在相隔20分钟的时间点测量时，环AMP和环GMP的组织含量显示出非常显著的变化[1]。尽管环核苷酸存在这些大的温度变化，但根据氧摄取、葡萄糖利用、烟酰胺核苷酸比、糖原周转、乳酸周转、丙氨酸输出[2，3]、蛋白质合成速率[1，4]、心率和收缩幅度[5]判断，心脏制剂明显处于稳态长达2小时。有人认为，细胞反馈调节系统可能会产生稳定的振荡，代谢稳态可以依赖于此[6]，此外，在无颗粒大鼠骨骼肌提取物中的腺嘌呤核苷酸和IMP浓度中观察到似乎与糖酵解振荡相关的振荡[7]。这种振荡现象是负责环核苷酸的变化的可能性进行了研究，通过测量在心脏和灌注所有嘌呤核苷酸，核苷和它们的降解产物在选定的时间点超过80分钟的灌注。在间隔10或20 min的时间点，ATP、ADP、GTP、环AMP、环GMP的含量、ATP/ADP比值和腺嘌呤核苷酸的总和存在高度显著性差异[5]。ATP/ADP比值、GTP和cAMP含量的变化规律与腺嘌呤核苷酸总量的变化规律不同。提取的总腺嘌呤核苷酸的非常大的净增加和减少既不能解释为Lowenstein嘌呤核苷酸循环的操作[7]，也不能解释为任何已知核苷酸前体、衍生物或聚合物的代谢，并且表明哺乳动物心脏中可能存在未被怀疑的大量嘌呤核苷酸储存形式[5]。本文报道，当心脏采样更频繁，非常有规律的统计学显着的时间变化，总腺嘌呤核苷酸含量被识别。此外，腺嘌呤核苷酸含量的变化反映了环GMP含量的反向变化。由于环GMP含量也出现响应总鸟嘌呤核苷酸的非同步变化，有人认为，鸟苷酸环化酶的活性可能是由细胞中的游离腺嘌呤核苷酸的水平进行调节。
While investigating amino acid incorporation into protein in Langendorf perfused hearts we made the surprising observation that the tissue contents of cyclic AMP and cyclic GMP showed very significant variations when measured at time points 20 rain apart during a 2 h perfusion period [1]. Despite these large temp oral variations in the cyclic nucleotides, the heart preparation is apparently in a steady-state for up to 2 h as judged by oxygen uptake, glucose utilization, nicotinamide nucleotide ratio, glycogen turnover, lactate turnover, alanine output [2, 3] protein-synthesis rate [1, 4], beat rate and contraction amplitude [5]. It had been suggested that cellular feedback-regulation systems might give rise to stable oscillations on which metabolic steady-states could rely [6] and moreover oscillations which appeared to be related to glycolytic oscillations had been observed in the concentrations of the adenine nucleotides and IMP in particle-free rat skeletal-muscle extracts [7]. The possibility that such oscillatory phenomena were responsible for the cyclic nucleotide variations was investigated by measuring in both hearts and perfusate all purine nucleotides, nucleosides and their degradation products at selected time points over 80 min of perfusion. Highly significant differences were found in the contents of ATP, ADP, GTP, cyclic AMP, cyclic GMP in the ATP/ADP ratio and in the sum of the adenine nucleotides at time points 10 or 20 min apart [5]. The ATP/ADP ratio and the contents of GTP and cyclic AMP showed an identical pattern of variation which was distinct from that of the total adenine nucleotide content. The very large nett increases and decreases in the total adenine nucleotides extracted could neither be explained as operation of Lowenstein's purine nucleotide cycle [7] nor as metabolism of any known nucleotide precursor, derivative or polymer and it was suggested that an unsuspected substantial storage form of purine nucleotide might exist in mammalian heart [5]. This paper reports that when hearts are sampled more frequently very regular statistically significant temporal variations in total adenine nucleotide content are discerned. Furthermore the changing adenine nucleotide content is mirrored by inverse alterations in the cyclic GMP content. Since the cyclic GMP content also appears to respond to the non-synchronous variations in total guanine nucleotide, it is argued that guanylate cyclase activity may be regulated by the level of free adenine nucleotide in the cell.