Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
Synapse. 2011 Dec;65(12):1368-72. doi: 10.1002/syn.20958. Epub 2011 Jun 17.
A number of published studies have questioned the serotonin neurotoxic potential of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and related drugs (fenfluramine, p-chloroamphetamine) based upon results from Western blot studies using a custom synthesized serotonin transporter (SERT) antibody that found no reduction in the abundance of a 50kDa protein after substituted amphetamine treatment. The purpose of this study was to collect Western blot data using the same SERT antibody used in those studies, but with positive and negative controls to identify the SERT protein signal. A 63-68 kDa band that had the regional distribution expected of rat brain SERT, was decreased by 5,7-DHT, and was absent in SERT KO animals was identified as the SERT protein. Significant, lasting decreases in the abundance of the 63-68 kDa band were evident in the rat brain after treatment with MDMA and related drugs (FEN, PCA). Thus, when the band corresponding to the SERT protein is identified in Western blots through the use of positive and negative controls, reduced abundance of the SERT protein can be readily demonstrated after substituted amphetamine treatment. These data provide further evidence of lasting loss of the SERT protein after exposure to MDMA and other substituted amphetamines.
许多已发表的研究基于使用自定义合成的血清素转运蛋白（SERT）抗体的 Western blot 研究结果，对 3,4-亚甲二氧基甲基苯丙胺（MDMA，“摇头丸”）和相关药物（芬氟拉明，对氯苯丙胺）的血清素神经毒性潜力提出了质疑，这些研究发现，在取代安非他命治疗后，50kDa 蛋白的丰度没有减少。本研究的目的是使用相同的 SERT 抗体收集 Western blot 数据，该抗体已用于这些研究，但使用阳性和阴性对照来鉴定 SERT 蛋白信号。鉴定出一种在大鼠脑中具有预期区域分布的 63-68 kDa 带，该带被 5,7-DHT 减少，并且在 SERT KO 动物中不存在，被鉴定为 SERT 蛋白。在大鼠脑中，经过 MDMA 和相关药物（FEN，PCA）处理后，63-68 kDa 带的丰度明显且持续减少。因此，当通过使用阳性和阴性对照在 Western blot 中鉴定出对应于 SERT 蛋白的条带时，在取代安非他命处理后，SERT 蛋白的丰度减少可以很容易地证明。这些数据进一步证明了暴露于 MDMA 和其他取代安非他命后 SERT 蛋白的持续丧失。
