Verdetti J, Aussedat J, Rossi A
J Physiol (Paris). 1980;76(7):693-8.
The dynamics of cardiac adenine and uracil nucleotides, following a subcutaneous injection of isoproterenol, was studied on the rat in vivo. The effect of continuous supply of adenosine, uridine, or ribose on the level of ATP and UTP was investigated on control rats and on isoproterenol-treated animals. The precursors were administered by continuous infusion (1 ml.h-1) into the superior caval vein. 1. ATP and UTP levels were decreased within one hour after a single dose of isoproterenol (5 mg.kg-1) (Fig. 1). 2. Then, the level of ATP rose slowly toward the control value. The normal level was not reached within 48 h (Fig. 1). 3. On the contrary, the initial drop in UTP concentration was followed by a rapid restoration. The control value was reached in 3 h, and then the UTP pool was increased to 180% of the normal level, 12 h after isoproterenol application. 4. As previously shown by other authors, the restoration of ATP was accelerated by a continuous supply of adenosine (37 micromoles per hour) or ribose (170 micromoles per hour) (Fig. 2). 5. The infusion of ribose (170 micromoles per hour) or uridine (41 micromoles per hour) completely suppressed the initial decrease in UTP level caused by beta-receptor stimulation. The further enlargement of the UTP pool was greatly enhanced by ribose or uridine (Fig. 3). 6. The infusion of adenosine was also positive on UTP regeneration. On the contrary, uridine had no effect on the ATP pool (Fig. 3). 7. When supplied to non-treated animals, all precursors caused an enhancement of the UTP level. Adenosine and ribose increased the ATP pool (Fig. 2 and 3). These results contribute to the comparison of the efficiency of the various pathways of cardiac nucleotide synthesis. They show that both de novo synthesis and salvage pathways are limited by the amount of precursors. The increase in UTP synthesis caused by ribose is consistent with the theory put forward for purines (ZIMMER et GERLACH, 1974) that phosphoribosyl-pyrophosphate availability limits the efficiency of de novo synthesis of nucleotides; it demonstrates that this concept is also true for de novo synthesis of pyrimidine nucleotides.
在大鼠体内研究了皮下注射异丙肾上腺素后心脏腺嘌呤和尿嘧啶核苷酸的动态变化。在对照大鼠和经异丙肾上腺素处理的动物身上，研究了持续供应腺苷、尿苷或核糖对ATP和UTP水平的影响。通过持续输注（1毫升/小时）将前体物质注入上腔静脉。1. 单次注射异丙肾上腺素（5毫克/千克）后1小时内，ATP和UTP水平降低（图1）。2. 然后，ATP水平缓慢上升至对照值。48小时内未恢复到正常水平（图1）。3. 相反，UTP浓度最初下降后迅速恢复。3小时内达到对照值，然后在应用异丙肾上腺素12小时后，UTP池增加到正常水平的180%。4. 如其他作者先前所示，持续供应腺苷（每小时37微摩尔）或核糖（每小时170微摩尔）可加速ATP的恢复（图2）。5. 输注核糖（每小时170微摩尔）或尿苷（每小时41微摩尔）可完全抑制由β受体刺激引起的UTP水平的初始下降。核糖或尿苷极大地增强了UTP池的进一步扩大（图3）。6. 输注腺苷对UTP再生也有积极作用。相反，尿苷对ATP池无影响（图3）。7. 当供应给未处理的动物时，所有前体物质都会导致UTP水平升高。腺苷和核糖增加了ATP池（图2和3）。这些结果有助于比较心脏核苷酸合成各种途径的效率。它们表明，从头合成和补救途径都受到前体物质数量的限制。核糖引起的UTP合成增加与嘌呤提出的理论（齐默尔和格尔拉赫，1974年）一致，即磷酸核糖焦磷酸的可用性限制了核苷酸从头合成的效率；这表明该概念对于嘧啶核苷酸的从头合成也适用。
