Deliconstantinos G, Tsakiris S
Biochem J. 1985 Jul 1;229(1):81-6. doi: 10.1042/bj2290081.
The evoked effects of the negatively charged drugs phenobarbital and barbituric acid, the positively charged imipramine, perphenazine and trifluoperazine, and the neutral primidone, on the synaptosome-associated acetylcholinesterase activity were studied. A marked increase in the enzyme activity was exhibited in the presence of low concentrations (up to 3 mM) of phenobarbital, barbituric acid and primidone. Higher concentrations (up to 10 mM), however, led to a progressive inhibition of the enzyme activity. However, the activity of the enzyme was not affected by imipramine, but it was decreased by perphenazine and trifluoperazine. Arrhenius plots of acetylcholinesterase activity exhibited a break point at 23.4 degrees C for the untreated (control) synaptosomes, which was shifted to around 16 degrees C in the synaptosomes treated with the charged drugs. The allosteric inhibition by F- of acetylcholinesterase was studied in control synaptosomes and in those treated with the charged drugs. Changes in the Hill coefficients in combination with changes in Arrhenius activation energy produced by the charged drugs would be expected if it is assumed that charged drugs 'fluidize' the synaptosomal plasma membranes.
研究了带负电荷的药物苯巴比妥和巴比妥酸、带正电荷的丙咪嗪、奋乃静和三氟拉嗪以及中性的扑米酮对突触体相关乙酰胆碱酯酶活性的诱发效应。在低浓度(高达3 mM)的苯巴比妥、巴比妥酸和扑米酮存在下,酶活性显著增加。然而,更高的浓度(高达10 mM)会导致酶活性逐渐受到抑制。然而,丙咪嗪对该酶的活性没有影响,但奋乃静和三氟拉嗪会使其活性降低。乙酰胆碱酯酶活性的阿伦尼乌斯曲线在未处理(对照)的突触体中于23.4℃处出现一个断点,在用带电荷药物处理的突触体中该断点移至约16℃。在对照突触体和用带电荷药物处理的突触体中研究了氟离子对乙酰胆碱酯酶的变构抑制作用。如果假设带电荷药物使突触体细胞膜“液化”,那么预计带电荷药物会导致希尔系数发生变化,并伴随阿伦尼乌斯活化能的改变。