Hossain Muhammad Mubarak, Suzuki Tadahiko, Sato Itaru, Takewaki Tadashi, Suzuki Koichi, Kobayashi Haruo
Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Morioka 020-8550, Japan.
Life Sci. 2005 Jul 1;77(7):795-807. doi: 10.1016/j.lfs.2005.01.014.
Our previous microdialysis study of freely moving rats demonstrated that 3 pyrethroids, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II) differentially modulate acetylcholine (ACh) release in the hippocampus. To better understand the mechanisms of their modulatory effects and also other effects on the cholinergic system in the brain, the activities of ACh hydrolyzing enzyme acetylcholinesterase (AChE), ACh synthesizing enzyme choline acetyltransferase (ChAT) and ACh synthesizing rate-limiting step, high-affinity choline uptake (HACU) were examined in the present study. The pyrethroids studied had no effect on AChE activity in the cortex, hippocampus and striatum. These pyrethroids had no significant effect on ChAT in the cortex and hippocampus, but striatal ChAT was increased at higher dosage (60 mg/kg) by all three compounds. Lineweaver-Burk analysis of hippocampal HACU revealed that the pyrethroids did not alter the Michaelis-Menten constant (Km) value but caused alteration of maximal velocity (Vmax). Allethrin (60 mg/kg) and cyhalothrin (20 and 60 mg/kg) decreased while deltamethrin (60 mg/kg) increased the Vmax for HACU. In vitro study showed that at higher concentrations (> or = 10(-) (6) M) allethrin and cyhalothrin reduced the hippocampal HACU but deltamethrin increased it. These results suggest that mechanisms of ACh synthesis are involved in the modulatory effects of the pyrethroids on ACh release and other cholinergic activities.
我们之前对自由活动大鼠进行的微透析研究表明，三种拟除虫菊酯，即丙烯菊酯（I型）、氯氟氰菊酯（II型）和溴氰菊酯（II型），对海马体中乙酰胆碱（ACh）的释放有不同程度的调节作用。为了更好地理解它们的调节作用机制以及对大脑胆碱能系统的其他影响，在本研究中检测了ACh水解酶乙酰胆碱酯酶（AChE）、ACh合成酶胆碱乙酰转移酶（ChAT）的活性以及ACh合成限速步骤——高亲和力胆碱摄取（HACU）。所研究的拟除虫菊酯对皮质、海马体和纹状体中的AChE活性没有影响。这些拟除虫菊酯对皮质和海马体中的ChAT没有显著影响，但在较高剂量（60 mg/kg）时，所有三种化合物都使纹状体中的ChAT增加。对海马体HACU的Lineweaver-Burk分析表明，拟除虫菊酯没有改变米氏常数（Km）值，但导致了最大速度（Vmax）的改变。丙烯菊酯（60 mg/kg）和氯氟氰菊酯（20和60 mg/kg）降低了HACU的Vmax，而溴氰菊酯（60 mg/kg）则增加了Vmax。体外研究表明，在较高浓度（≥10^(-6) M）时，丙烯菊酯和氯氟氰菊酯降低了海马体HACU，但溴氰菊酯增加了HACU。这些结果表明，ACh合成机制参与了拟除虫菊酯对ACh释放和其他胆碱能活动的调节作用。
