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大鼠药物性帕金森综合征——帕金森综合征生化研究的一个模型。III. 用利血平或吩噻嗪预处理的大鼠脑和肝脏氨基酸中D-葡萄糖-14C(U)的掺入。

Drug-induced parkinsonism in the rat- a model for biochemical investigation of the parkinson-syndrome. III. The incorporation of D-glucose-14C(U) in amino acids of brain and liver from rats pretreated with reserpine or with phenothiazines.

作者信息

Gründig E, Raheem K A, Salvenmoser F, Schedl R, Weiss J

出版信息

Psychopharmacology (Berl). 1976 May 5;47(1):111-8. doi: 10.1007/BF00428712.

Abstract

Following treatment with reserpine or alternatively with a combination of phenothiazines (Randolektil, Majeptil) a drug-induced parkinsonoid reaction was provoked in rats. Twenty min before decapitation, 18 muCi d-glucose-14C(U) was administered intravenously. Concentration and radioactivities of glutamic acid (glu), glutamine (gln), serine (ser), and glycine (gly) were assayed in some regions of brain and in liver. Separation was performed by a combination of paper electrophoresis and chromatography or by an automatic amino acid analyzer. 1 After reserpine, the concentrations of serine and glycine were increased ten-fold while their specific activities decreased by the same factor. The interconversion serine-glycine was not affected. The concentration of glutamic acid was reduced while its specific activity remained constant. 2. After phenothiazines, the concentrations of serine and glycine in brain were also increased but their specific activities were decreased to a different degree. This indicates an additional effect on the serine-synthesis from glucose. The interconversion serine-glycine was also altered. The concentration of glutamic acid was decreased but specific activity was constant except in the thalamus region tested. 3. The influence of both treatments on amino acid turnover in liver differed from the observed impairment of brain metabolism. 4. Possible correlations between the changes in amino acid metabolism, catecholamines, and the neurologic parkinsonian symptoms are discussed.

摘要

用利血平或吩噻嗪类药物(兰多雷克替尔、马耶普替尔)联合治疗后,在大鼠中引发了药物性帕金森样反应。在断头前20分钟,静脉注射18微居里的d-葡萄糖-14C(U)。测定了大脑某些区域和肝脏中谷氨酸(glu)、谷氨酰胺(gln)、丝氨酸(ser)和甘氨酸(gly)的浓度及放射性。通过纸电泳和色谱法相结合或自动氨基酸分析仪进行分离。1. 利血平处理后,丝氨酸和甘氨酸的浓度增加了10倍,而它们的比活性降低了相同的倍数。丝氨酸-甘氨酸的相互转化未受影响。谷氨酸的浓度降低,但其比活性保持不变。2. 吩噻嗪类药物处理后,大脑中丝氨酸和甘氨酸的浓度也增加,但它们的比活性降低程度不同。这表明对葡萄糖合成丝氨酸有额外影响。丝氨酸-甘氨酸的相互转化也发生了改变。谷氨酸的浓度降低,但除测试的丘脑区域外,比活性保持不变。3. 两种处理对肝脏氨基酸周转的影响与观察到的大脑代谢损害不同。4. 讨论了氨基酸代谢变化、儿茶酚胺与帕金森病神经症状之间可能的相关性。

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