Lim D K, Porter A B, Hoskins B, Ho I K
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Toxicol Appl Pharmacol. 1987 Sep 30;90(3):477-89. doi: 10.1016/0041-008x(87)90140-2.
Rats were treated with diisopropylfluorophosphate (DFP) acutely and daily for 14 days. The total, free, and bound acetylcholine (ACh) levels were monitored in striatum, hippocampus, and frontal cortex after DFP administration. Thirty minutes after daily administration of DFP, the total and free ACh levels were significantly increased and remained constant after each successive dose. The bound ACh levels in striatum and frontal cortex were also significantly increased; however, they were comparable to control levels after the 14th injection of DFP. The total ACh levels 30 min after a challenge dose of 2 mg/kg DFP in saline and DFP subacutely treated rats were significantly increased in hippocampus (34 and 76%) and frontal cortex (49 and 64%) and were not significantly different between the two groups. However, the level of total ACh in striatum was increased less in the tolerant rats (10%) than in the acutely treated rats (36%). The levels of free and bound ACh after acute administration of 2 mg/kg DFP were markedly increased in three brain regions. After subacute administration, the levels of bound ACh were significantly increased in hippocampus (84%) and frontal cortex (40%); however, that in striatum did not change. The increase in the bound ACh level in the subacute treatment group was less than that in acutely treated rats in all three brain regions; however, the duration of the elevation of the free ACh in striatum was shorter in subacutely treated rats. These results suggest that the presynaptic cholinergic storage sites for ACh might be changed during subacute administration of DFP.
大鼠被急性给予二异丙基氟磷酸酯（DFP），并持续每日给药14天。在给予DFP后，监测纹状体、海马体和额叶皮质中总乙酰胆碱（ACh）、游离ACh和结合ACh的水平。每日给予DFP 30分钟后，总ACh和游离ACh水平显著升高，且在每次连续给药后保持恒定。纹状体和额叶皮质中的结合ACh水平也显著升高；然而，在第14次注射DFP后，它们与对照水平相当。在生理盐水和亚急性DFP处理的大鼠中，给予2 mg/kg DFP激发剂量30分钟后，海马体（分别为34%和76%）和额叶皮质（分别为49%和64%）中的总ACh水平显著升高，两组之间无显著差异。然而，耐受性大鼠纹状体中的总ACh水平升高幅度（10%）低于急性处理大鼠（36%）。急性给予2 mg/kg DFP后，三个脑区的游离ACh和结合ACh水平均显著升高。亚急性给药后，海马体（84%）和额叶皮质（40%）中的结合ACh水平显著升高；然而，纹状体中的结合ACh水平未发生变化。亚急性处理组中结合ACh水平的升高幅度在所有三个脑区均低于急性处理大鼠；然而，亚急性处理大鼠纹状体中游离ACh升高的持续时间较短。这些结果表明，在亚急性给予DFP期间，ACh的突触前胆碱能储存位点可能发生了变化。
