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大鼠脑中二甲氨基乙醇(迪安醇)的代谢及其对乙酰胆碱合成的影响。

Dimethylaminoethanol (deanol) metabolism in rat brain and its effect on acetylcholine synthesis.

作者信息

Jope R S, Jenden D J

出版信息

J Pharmacol Exp Ther. 1979 Dec;211(3):472-9.

PMID:512912
Abstract

Specific methods utilizing combined gas chromatography mass spectrometry were used to measure the metabolism of [2H6] deanol and its effects on acetylcholine concentration in vitro and in vivo. In vitro [2H6]deanol was rapidly taken up by rat brain synaptosomes, but was neither methylated nor acetylated. [2H6]Deanol was a weak competitive inhibitor of the high affinity transport of [2H4]choline, thus reducing the synthesis of [2H4]acetylcholine. In vivo [2H6]deanol was present in the brain after i.p. or p.o. administration, but was not methylated or acetylated. Treatment of rats with [2H6]deanol significantly increased the concentration of choline in the plasma and brain but did not alter the concentration of acetylcholine in the brain. Treatment of rats with atropine (to stimulate acetylcholine turnover) or with hemicholinium-3 (to inhibit the high affinity transport of choline) did not reveal any effect of [2H6]deanol on acetylcholine synthesis in vivo. However, since [2H6]deanol did increase brain choline, it may prove therapeutically useful when the production of choline is reduced or when the utilization of choline for the synthesis of acetylcholine is impaired.

摘要

采用特定的联用气相色谱 - 质谱分析法来测定[2H6]二甲氨基乙醇的代谢及其对体内外乙酰胆碱浓度的影响。在体外,[2H6]二甲氨基乙醇被大鼠脑突触体迅速摄取,但既未发生甲基化也未发生乙酰化。[2H6]二甲氨基乙醇是[2H4]胆碱高亲和力转运的弱竞争性抑制剂,从而减少了[2H4]乙酰胆碱的合成。在体内,腹腔注射或口服给药后,[2H6]二甲氨基乙醇存在于脑中,但未发生甲基化或乙酰化。用[2H6]二甲氨基乙醇处理大鼠可显著提高血浆和脑中胆碱的浓度,但并未改变脑中乙酰胆碱的浓度。用阿托品(刺激乙酰胆碱周转)或用半胱氨酸 - 3(抑制胆碱的高亲和力转运)处理大鼠,未发现[2H6]二甲氨基乙醇对体内乙酰胆碱合成有任何影响。然而,由于[2H6]二甲氨基乙醇确实增加了脑胆碱,当胆碱生成减少或胆碱用于合成乙酰胆碱的利用受损时,它可能在治疗上有用。

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