Villa R F, Arnaboldi R, Gorini A, Geroldi D
Department of Science, University of Pavia, Italy.
Farmaco. 1989 Feb;44(2):215-26.
The maximum rate (Vmax) of some mitochondrial enzymatic activities related to energy transduction (citrate synthase, malate dehydrogenase, NADH-cytochrome c reductase (as total activity), cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase) were evaluated in non-synaptic (free) and synaptic mitochondria from rat brain hippocampus. Three types of mitochondria were isolated from rats subjected to single i.p. treatments with piracetam (300 mg.kg-1) or with clonidine (750 micrograms.kg-1). With respect to the enzymatic pattern of three types of non-synaptic and synaptic mitochondria, in hippocampus a different maximum rate of both NADH-cytochrome c reductase and cytochrome oxidase was observed, these activities in particular being lowest in the "synaptic heavy" mitochondrial subfraction than in the "synaptic light" one; in addition, other enzyme activities are different in the "free" as compared to both the "light" and "heavy" mitochondria. This confirms that in various types of brain mitochondria a different metabolic machinery exists. Acute treatment with piracetam decreased citrate synthase, glutamate dehydrogenase, NADH-cytochrome c reductase and cytochrome oxidase activities only in the "heavy" mitochondria obtained from synaptosomes. Acute treatment with clonidine decreased the citrate synthase, NADH-cytochrome c reductase and cytochrome oxidase activities only in the same type of mitochondria, i.e. synaptic "heavy" mitochondria. However, this drug increased the same enzymatic activities in "free" mitochondria, some of them being increased or decreased in "light" intrasynaptic ones. Therefore in vivo administration of piracetam mainly affects some specific enzyme activities (suggesting a specific molecular trigger mode of action) of the intrasynaptic mitochondria (suggesting a specific subcellular trigger site of action), the effect on enzyme activities by clonidine being more complex.
在大鼠脑海马体的非突触（游离）线粒体和突触线粒体中，评估了一些与能量转导相关的线粒体酶活性（柠檬酸合酶、苹果酸脱氢酶、NADH - 细胞色素c还原酶（总活性）、细胞色素氧化酶）以及氨基酸代谢（谷氨酸脱氢酶）的最大反应速率（Vmax）。从经腹腔注射吡拉西坦（300 mg·kg⁻¹）或可乐定（750 μg·kg⁻¹）单次处理的大鼠中分离出三种类型的线粒体。关于三种类型的非突触和突触线粒体的酶模式，在海马体中观察到NADH - 细胞色素c还原酶和细胞色素氧化酶的最大反应速率不同，特别是这些活性在“突触重”线粒体亚组分中比在“突触轻”亚组分中更低；此外，与“轻”和“重”线粒体相比，“游离”线粒体中的其他酶活性也不同。这证实了在各种类型的脑线粒体中存在不同的代谢机制。吡拉西坦急性处理仅降低了从突触体获得的“重”线粒体中的柠檬酸合酶、谷氨酸脱氢酶、NADH - 细胞色素c还原酶和细胞色素氧化酶活性。可乐定急性处理仅降低了同一类型线粒体即突触“重”线粒体中的柠檬酸合酶、NADH - 细胞色素c还原酶和细胞色素氧化酶活性。然而，这种药物增加了“游离”线粒体中的相同酶活性，其中一些在“轻”突触内线粒体中增加或降低。因此，体内给予吡拉西坦主要影响突触内线粒体的一些特定酶活性（表明特定的分子触发作用模式），（表明特定的亚细胞触发作用位点），可乐定对酶活性的影响更为复杂。
