抗坏血酸对[3H]MPP +、[3H]多巴胺和[14C]GABA突触体摄取的影响。

Effect of ascorbic acid on the synaptosomal uptake of [3H]MPP+, [3H]dopamine, and [14C]GABA.

作者信息

Sershen H, Debler E A, Lajtha A

出版信息

J Neurosci Res. 1987;17(3):298-301. doi: 10.1002/jnr.490170315.

Abstract

The effects of ascorbic acid on the synaptosomal uptake of [3H]MPP+, [3H]dopamine, and [14C]GABA were examined in attempts to understand the mechanism of ascorbic acid attenuation of MPTP neurotoxicity. [3H]Dopamine uptake was increased at lower levels (0.01 and 0.1 mM) and decreased at higher levels (10 mM) of ascorbic acid. Ascorbic acid inhibited [3H]MPP+ uptake (IC50 = 0.1 mM) and [14C]GABA uptake (IC50 = 10 mM). Washout of ascorbic acid restored uptake of [3H]dopamine and [3H]MPP+, suggesting that ascorbic-acid-induced lipid peroxidation was not involved in the effect on uptake. In addition to the possible involvement of antioxidant mechanisms in the in vivo attenuation of the neurotoxicity of MPTP by ascorbic acid, the present results indicate a direct effect of ascorbic acid in inhibiting the uptake of MPP+ into dopaminergic nerve terminals.

摘要

为了理解抗坏血酸减轻MPTP神经毒性的机制，研究了抗坏血酸对[3H]MPP⁺、[3H]多巴胺和[14C]GABA突触体摄取的影响。较低水平（0.01和0.1 mM）的抗坏血酸会增加[3H]多巴胺的摄取，而较高水平（10 mM）的抗坏血酸则会降低其摄取。抗坏血酸抑制[3H]MPP⁺摄取（IC50 = 0.1 mM）和[14C]GABA摄取（IC50 = 10 mM）。洗脱抗坏血酸可恢复[3H]多巴胺和[3H]MPP⁺的摄取，这表明抗坏血酸诱导的脂质过氧化与摄取效应无关。除了抗氧化机制可能参与抗坏血酸在体内减轻MPTP神经毒性外，本研究结果还表明抗坏血酸对抑制MPP⁺摄取到多巴胺能神经末梢有直接作用。