Acetate-dependent mechanisms of inborn tolerance to ethanol.
Acetate-dependent mechanisms of inborn tolerance to ethanol.
复制标题
乙醇先天耐受的乙酸依赖机制。
DOI：
10.1093/alcalc/agr014
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Deitrich,RichardA
中科院分区：
文献类型：
--
作者：
Zimatkin,SergeyM;Oganesian,NikolayA;Kiselevski,YuryV;Deitrich,RichardA
目的：阐明乙酸盐在乙醇初始（先天）耐受的神经化学机制中的作用。方法：使用对乙醇催眠作用具有低和高先天耐受性的大鼠。检测脑区匀浆（额顶叶皮质、下丘脑、纹状体、延髓）和脑皮质突触体中乙酸、乙酰辅酶A、乙酰胆碱（AcH）的水平、丙酮酸脱氢酶（PDG）和乙酰辅酶A合成酶的活性。乙酸盐水平和乙酰辅酶A合成酶活性，但乙酰辅酶A水平和PDG活性较低。在耐受大鼠的大脑皮层突触体中，与不耐受的动物相比，丙酮酸氧化速率以及乙酰辅酶A和AcH合成的含量较低。在培养基中添加乙酸盐显着增加了耐受动物突触体中的 AcH 合成，但不耐受动物的突触体中 AcH 合成却没有。钙离子刺激耐受动物突触体释放的 AcH 量是不耐受动物的两倍。乙酸消除了钙离子对不耐受大鼠突触体中 AcH 释放的刺激作用，但不能消除耐受动物的突触体。结果表明，在醋酸存在的情况下，耐受组突触体中AcH的量子释放量比不耐受组高6.5倍。结论：对乙醇催眠作用具有高先天耐受性的大鼠的大脑皮层能够更好地利用醋酸进行乙酰辅酶A和AcH的合成，并且能够抵抗醋酸对钙刺激AcH释放的抑制作用。它表明了对乙醇初始耐受的代谢和胆碱能机制。
Aims:To clarify the role of acetate in neurochemical mechanisms of the initial (inborn) tolerance to ethanol.Methods:Rats with low and high inborn tolerance to hypnotic effect of ethanol were used. In the brain region homogenates (frontal and parietal cortex, hypothalamus, striatum, medulla oblongata) and brain cortex synaptosomes, the levels of acetate, acetyl-CoA, acetylcholine (AcH), the activity of pyruvate dehydrogenase (PDG) and acetyl-CoA synthetase were examined.Results:It has been found that brain cortex of rats with high tolerance to hypnotic effect of ethanol have higher level of acetate and activity of acetyl-CoA synthetase, but lower level of acetyl-СCoA and activity of PDG. In brain cortex synaptosomes of tolerant rats, the pyruvate oxidation rate as well as the content of acetyl-CoA and AcH synthesis were lower when compared with intolerant animals. The addition of acetate into the medium significantly increased the AcH synthesis in synaptosomes of tolerant, but not of intolerant animals. Calcium ions stimulated the AcH release from synaptosomes twice as high in tolerant as in intolerant animals. Acetate eliminated the stimulating effect of calcium ions upon the release of AcH in synaptosomes of intolerant rats, but not in tolerant animals. As a result, the quantum release of AcH from synaptosomes in the presence of acetate was 6.5 times higher in tolerant when compared with intolerant rats.Conclusion:The brain cortex of rats with high inborn tolerance to hypnotic effect of ethanol can better utilize acetate for the acetyl-CoA and AcH synthesis, as well as being resistant to inhibitory effect of acetate to calcium-stimulated release of AcH. It indicates the metabolic and cholinergic mechanisms of the initial tolerance to ethanol.