Simintzi Irene, Schulpis Kleopatra H, Angelogianni Panagoula, Liapi Charis, Tsakiris Stylianos
Department of Experimental Physiology, Medical School, University of Athens, P.O. Box 65257, GR-15401 Athens, Greece.
Pharmacol Res. 2007 Aug;56(2):155-9. doi: 10.1016/j.phrs.2007.05.003. Epub 2007 May 13.
Neurological disturbances have been implicated with aspartame (ASP) consumption and the cholinergic system with acetylcholinesterase (AChE) seems actively involved.
To evaluate the effect of ASP and its metabolites on rat hippocampal AChE activity.
Hippocampal homogenate or pure enzyme AChE (eel E. electricus) was incubated with the sum or each of ASP components, phenylalanine (Phe), aspartic acid (asp) and methanol (MeOH) for 1h at 37 degrees C. AChE activity was measured spectrophotometrically.
Incubation of rat tissue or pure enzyme with the sum of ASP metabolites in concentrations in CSF (the concentrations were calculated according to the CSF/plasma concentration ratios) following 150 or 200mgkg(-1) of ASP consumption, resulted in significant enzyme activity reductions of 25 and 31% for hippocampal AChE and 11% (p<0.01) and 19% for pure enzyme, respectively. Aspartic acid concentrations of 0.42 or 0.56mM significantly reduced the enzyme activities by 13 and 20% for hippocampal AChE and 15 and 18% for pure enzyme, respectively. Phe concentrations of 0.042 or 0.083mM decreased the enzyme activity by 12% (p<0.01) and 20% (p<0.001) for hippocampal AChE and 15 and 18% (p<0.001) for pure enzyme, respectively. Methanol concentrations of 0.60 or 0.80mM remarkably inhibited hippocampal AChE by about 18 and 22% and pure enzyme by about 14 and 20%, respectively.
Low concentrations of ASP components had no effect on hippocampal and pure AChE activity, whereas high or toxic concentrations remarkably decreased both enzyme activities. Muscarinic symptoms may be related to the latter concentrations of ASP metabolites.
神经功能紊乱与阿斯巴甜(ASP)的摄入有关,且胆碱能系统以及乙酰胆碱酯酶(AChE)似乎积极参与其中。
评估ASP及其代谢产物对大鼠海马体AChE活性的影响。
将海马体匀浆或纯酶AChE(电鳗的AChE)与ASP的总和或各组分,即苯丙氨酸(Phe)、天冬氨酸(asp)和甲醇(MeOH)在37℃下孵育1小时。采用分光光度法测定AChE活性。
在摄入150或200mg/kg的ASP后,将大鼠组织或纯酶与脑脊液中ASP代谢产物总和(根据脑脊液/血浆浓度比计算浓度)孵育,导致海马体AChE的酶活性分别显著降低25%和31%,纯酶的酶活性分别降低11%(p<0.01)和19%。0.42或0.56mM的天冬氨酸浓度分别使海马体AChE的酶活性显著降低13%和20%,纯酶的酶活性分别降低15%和18%。0.042或0.083mM的Phe浓度分别使海马体AChE的酶活性降低12%(p<0.01)和20%(p<0.001),纯酶的酶活性分别降低15%和18%(p<0.001)。0.60或0.80mM的甲醇浓度分别使海马体AChE显著抑制约18%和22%,纯酶显著抑制约14%和20%。
低浓度的ASP组分对海马体和纯AChE活性无影响,而高浓度或有毒浓度会显著降低两种酶的活性。毒蕈碱样症状可能与后一种浓度的ASP代谢产物有关。