Actinomycin D Inhibition of the Adaptation of Renal Glutamine-deaminating Enzyme in the Rat
Actinomycin D Inhibition of the Adaptation of Renal Glutamine-deaminating Enzyme in the Rat
复制标题
放线菌素 D 对大鼠肾谷氨酰胺脱氨酶适应的抑制作用
DOI：
10.1038/2051330a0
复制
发表时间：
1965
期刊：
影响因子：
64.8
通讯作者：
L. Goldstein
中科院分区：
文献类型：
--
作者：
L. Goldstein
先前的研究表明，代谢性酸中毒会导致大鼠1,2和豚鼠3肾脏中谷氨酰胺酶和谷氨酰胺转氨酶-ω-酰胺酶（GTA）的活性显着增加。这些变化与大鼠 2,4 和豚鼠 3 肾氨排泄对酸中毒的适应有关，并且被认为与之相关。肾谷氨酰胺酶对代谢性酸中毒的反应不是由肾上腺5或底物谷氨酰胺6介导的，并且仅限于肾脏5。 Goldstein 和 Kensler5 发现给豚鼠注射乙硫氨酸可抑制酸诱导的肾谷氨酰胺酶活性升高，我们认为代谢性酸中毒会刺激肾细胞合成谷氨酰胺酶。这种刺激发生的方式尚不清楚。 Kroeger7 最近报道称，昆虫摇蚊 (Chironomus thummi) 分离的唾液腺中的电解质平衡的改变，对这些腺体中发现的巨型染色体的基因活性（RNA 合成）产生了显着且特定的变化。代谢性酸中毒和随之而来的电解质平衡变化可能对肾细胞中的 UNA 合成产生类似的影响。 Actinomycin D 是一种抗生素，可干扰细菌和动物细胞中 DNA 依赖性 RNA 合成8，已被证明可以抑制大鼠肾脏中 RNA 的合成9。因此，在大鼠中研究了这种抗生素对肾谷氨酰胺酶、GTA 和氨排泄对代谢性酸中毒反应的影响。
PREVIOUS investigations have shown that metabolic acidosis leads to significant increases in the activities of glutaminase and glutamine transaminase-ω-amidase (GTA) in kidneys of rats1,2 and guinea-pigs3. These changes are associated with, and thought to be related to, the adaptation of renal ammonia excretion to acidosis in the rat2,4 and guinea-pig3. The response of renal glutaminase to metabolic acidosis is not mediated by the adrenal gland5 or substrate, glutamine6, and is restricted to the kidneys5. Goldstein and Kensler5 found that administration of ethionine to guinea-pigs inhibited the acid-induced rise in renal glutaminase activity, and we suggested that metabolic acidosis stimulates the synthesis of glutaminase by renal cells. The manner in which this stimulation occurs is unknown. Kroeger7 has recently reported that alterations in the electrolyte balance of the medium bathing isolated salivary glands of the insect Chironomus thummi produced marked and specific changes in the gene activities (RNA synthesis) of the giant chromosomes found in these glands. Metabolic acidosis and the accompanying changes in electrolyte balance might have similar effects on UNA synthesis in renal cells. Actinomycin D, an antibiotic which interferes with the DNA-dependent synthesis of RNA in bacterial and animal cells8, has been shown to inhibit the synthesis of RNA in rat kidneys9. The effects of this antibiotic on the responses of renal glutaminase, GTA and ammonia excretion to metabolic acidosis were therefore investigated in the rat.