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[左旋多巴对与大鼠血浆和脑中色氨酸浓度相关的脑血清素代谢的影响]

[Effect of L-DOPA on brain serotonin metabolism related to tryptophan concentrations in plasma and brain of rats].

作者信息

Kohno Y

出版信息

Nihon Yakurigaku Zasshi. 1981 Mar;77(3):281-93.

PMID:6188670
Abstract

Changes in tryptophan (Trp) concentrations in the peripheral and brain tissues and their influences on brain serotonin (5-HT) metabolism were investigated after i.p. administrations of L-DOPA alone and in combination with Ro4-4602 in male Wistar rats. L-DOPA alone elicited marked increases of both plasma free and liver Trp levels, and a slight increase of brain Trp level. Concomitant application of L-DOPA and Ro4-4602 did not change peripheral Trp concentrations but did reduce brain Trp level. Brain 5-HT levels were reduced in proportion to the increase of dopamine (DA) level by L-DOPA alone and Ro4-4602 plus L-DOPA. A marked increase of 5-HIAA level was exhibited by L-DOPA alone, while Ro4-4602 plus L-DOPA increased 5-HIAA levels slightly despite a marked decrease in 5-HT levels. The decrease of 5-HT and increase of 5-HIAA levels were also observed after administration of L-DOPA to neonatal rats in which the brain tryptophan hydroxylase was considered to be saturated. These results suggest that changes in 5-HT metabolism after L-DOPA injections are not only caused by DA which displaces 5-HT from vesicular stores, but also by changes in Trp concentrations in the plasma and brain which alter 5-HT synthesis and turnover.

摘要

在雄性Wistar大鼠腹腔注射左旋多巴(L-DOPA)单独给药以及与Ro4-4602联合给药后,研究了外周和脑组织中色氨酸(Trp)浓度的变化及其对脑血清素(5-HT)代谢的影响。单独使用L-DOPA可使血浆游离Trp水平和肝脏Trp水平显著升高,脑Trp水平略有升高。同时应用L-DOPA和Ro4-4602不会改变外周Trp浓度,但会降低脑Trp水平。单独使用L-DOPA以及Ro4-4602加L-DOPA时,脑5-HT水平会随着多巴胺(DA)水平的升高而相应降低。单独使用L-DOPA可使5-HIAA水平显著升高,而Ro4-4602加L-DOPA尽管5-HT水平显著降低,但5-HIAA水平略有升高。在给脑色氨酸羟化酶被认为已饱和的新生大鼠注射L-DOPA后,也观察到了5-HT的降低和5-HIAA水平的升高。这些结果表明,L-DOPA注射后5-HT代谢的变化不仅是由DA从囊泡储存中置换5-HT引起的,还与血浆和脑中Trp浓度的变化有关,这些变化会改变5-HT的合成和周转。

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