Wecker L, Cawley G, Rothermel S
Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112.
J Neurochem. 1989 Feb;52(2):568-75. doi: 10.1111/j.1471-4159.1989.tb09157.x.
The main objective of these studies was to determine whether the acute administration of choline to rats provides supplemental precursor that can be used to support acetylcholine synthesis when the demand for choline is increased by increasing neurotransmitter release. For these experiments, hippocampal and striatal slices were prepared form rats that had received saline or an acute injection of choline. Slices were incubated in a choline-free buffer containing 4.74-35 mM KCl, and acetylcholine synthesis and release and choline production were measured. The initial tissue contents of acetylcholine and choline did not differ between experimental groups for either brain region. When hippocampal slices from the controls were incubated for 10 min with depolarizing concentrations of KCl, acetylcholine release increased and the tissue content decreased in a concentration-dependent fashion; no net synthesis of acetylcholine occurred. In contrast, hippocampal slices from the choline-injected animals maintained their tissue content in the presence of high concentrations of KCl, despite an increase in acetylcholine release that was similar in magnitude to that of the controls; positive net synthesis of acetylcholine resulted. Although the molar concentration of choline achieved in the incubation media at the end of the 10-min period did not differ between groups, the mobilization of free choline from bound stores was significantly greater in hippocampal slices from the choline-injected group than the controls. In addition, the synthesis of acetylcholine by hippocampal slices from the choline-injected group was prevented by the presence of hemicholinium-3 (1 microM) in the media.(ABSTRACT TRUNCATED AT 250 WORDS)
这些研究的主要目的是确定对大鼠急性给予胆碱是否能提供补充前体,以便在通过增加神经递质释放而使胆碱需求增加时,该前体可用于支持乙酰胆碱的合成。对于这些实验,从接受过生理盐水或急性注射胆碱的大鼠制备海马体和纹状体切片。将切片置于含有4.74 - 35 mM氯化钾的无胆碱缓冲液中孵育,并测量乙酰胆碱的合成、释放以及胆碱的生成。对于任一脑区,实验组之间乙酰胆碱和胆碱的初始组织含量均无差异。当将对照组的海马体切片用去极化浓度的氯化钾孵育10分钟时,乙酰胆碱释放增加,且组织含量以浓度依赖方式降低;未发生乙酰胆碱的净合成。相反,来自注射胆碱动物的海马体切片在高浓度氯化钾存在的情况下保持其组织含量,尽管乙酰胆碱释放增加的幅度与对照组相似;但产生了乙酰胆碱的正净合成。尽管在10分钟孵育期结束时各实验组孵育介质中胆碱的摩尔浓度无差异,但来自注射胆碱组的海马体切片中游离胆碱从结合储存库的动员显著大于对照组。此外,介质中存在半胱氨酸 - 3(1 microM)可阻止来自注射胆碱组的海马体切片合成乙酰胆碱。(摘要截取自250词)