Renal metabolic response to acid-base changes. II. The early effects of metabolic acidosis on renal metabolism in the rat.
Renal metabolic response to acid-base changes. II. The early effects of metabolic acidosis on renal metabolism in the rat.
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肾脏对酸碱变化的代谢反应。
DOI：
10.1172/jci106314
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发表时间：
1970
期刊：
影响因子：
--
通讯作者：
G. Alleyne
中科院分区：
文献类型：
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作者：
G. Alleyne
在通过口服氯化铵导致酸中毒的大鼠中研究了早期肾脏代谢反应。喂食氯化铵后2小时，已经出现明显的酸中毒。摄入氯化铵后尿氨也增加，并在 1(1/2) 小时显着升高。肾皮质切片的体外糖异生作用在2小时时增加，此后稳定增加。相同切片的氨产生量在2小时时也有所增加，但此后下降，并在6小时时降低至虽然高于对照的水平，但低于从仅酸中毒2小时的大鼠获得的水平。在酸中毒的前 6 小时内，体外糖异生和大鼠肾切片产生的氨之间没有相关性，但在氯化铵喂养 48 小时后，这两个过程显着相关。以谷氨酰胺和琥珀酸作为底物可证明肾糖异生的早期增加。酸中毒 4-6 小时后，磷酸烯醇丙酮酸羧激酶的活性增加。在此期间，肾 RNA 合成减少，如 RNA 中乳清酸-(5)H 摄取减少所示。还在诱导酸中毒后的不同时间测量速冻肾脏中的代谢中间体。天冬氨酸立即上升，α-酮戊二酸和苹果酸水平下降。对照组和酸中毒大鼠之间的丙酮酸或乳酸水平或乳酸：丙酮酸比率没有任何差异。酸中毒 6 小时后磷酸烯醇丙酮酸显着升高。所有数据表明，糖异生增加是对代谢性酸中毒的早期反应，并且将通过利用抑制谷氨酰胺酶 I 的谷氨酸促进氨的产生。代谢中间体的变化模式也可以解释为表明不仅糖异生增强，而且作为对代谢性酸中毒的早期反应的一部分，谷氨酰胺酶 II 的活性可能显着增加。
The early renal metabolic response was studied in rats made acidotic by oral feeding of ammonium chloride. 2 hr after feeding of ammonium chloride there was already significant acidosis. Urinary ammonia also increased after ammonium chloride ingestion and at 1(1/2) hr was significantly elevated. In vitro gluconeogenesis by renal cortical slices was increased at 2 hr and thereafter increased steadily. Ammonia production by the same slices was also increased at 2 hr, but thereafter fell and at 6 hr had decreased to levels which, although higher than those of the control, were lower than those obtained from the rats acidotic for only 2 hr. There was no correlation between in vitro gluconeogenesis and ammonia production by kidney slices from rats during the first 6 hr of acidosis, but after 48 hr of ammonium chloride feeding, these two processes were significantly correlated. The early increase in renal gluconeogenesis was demonstrable with both glutamine and succinate as substrates. The activity of the enzyme phosphoenolpyruvate carboxykinase was increased after 4-6 hr of acidosis. During this time there was a decrease in renal RNA synthesis as shown by decreased uptake of orotic acid-(5)H into RNA. Metabolic intermediates were also measured in quick-frozen kidneys at varying times after induction of acidosis. There was an immediate rise in aspartate and a fall in alpha-ketoglutarate and malate levels. There was never any difference in pyruvate or lactate levels or lactate:pyruvate ratios between control and acidotic rats. Phosphoenolpyruvate rose significantly after 6 hr of acidosis. All the data indicate that increased gluconeogenesis is an early response to metabolic acidosis and will facilitate ammonia production by utilization of glutamate which inhibits the glutaminase I enzyme. The pattern of change in metabolic intermediates can also be interpreted as showing that there is not only enhanced gluconeogenesis, but also that there may be significant increase of activity of glutaminase II as part of the very early response to metabolic acidosis.