Effects of amphetamines on regional tryptophan hydroxylase activity and synaptosomal conversion of tryptophan to 5-hydroxytryptamine in rat brain.
Effects of amphetamines on regional tryptophan hydroxylase activity and synaptosomal conversion of tryptophan to 5-hydroxytryptamine in rat brain.
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安非他明对大鼠脑中区域色氨酸羟化酶活性和色氨酸突触体转化为 5-羟色胺的影响。
DOI：
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发表时间：
1974
影响因子：
3.5
通讯作者：
M. Geyer
中科院分区：
文献类型：
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作者：
S. Knapp;A. Mandell;M. Geyer
急性给药d -安非他明、甲基苯丙胺、对-氯非他明和l -安非他明可降低大鼠纹状体突触体中色氨酸向5-羟色胺（5-HT）的转化。d -安非他明在降低转化活性方面的效力大约是l -安非他明的两倍。相反，芬氟拉明增加了神经末梢5-HT生物合成指数。当在研究转化活性的同一组织制剂中测量时，所研究的安非他明均未影响突触体对14c - l -色氨酸的摄取。d -安非他明使纹状体突触体中可溶性色氨酸羟化酶活性降低，其程度与转化活性降低相同，这是导致转化活性降低的原因。d -安非他明后，外侧中脑色氨酸羟化酶活性的下降程度与神经末梢相同，但外侧中脑的下降先于神经末梢。d -安非他明对中脑内侧区域的酶活性没有影响。在100µM的浓度下，没有一种安非他明对体外色氨酸羟化酶活性有明显的影响。在体外100µM和体内10 mg/kg剂量下，大鼠体内的两种主要安非他命代谢物对-羟安非他命和对-羟去甲麻黄碱不影响区域色氨酸羟化酶活性或色氨酸向5-羟色胺的突触体转化。安非他明引起的神经末梢5-羟色胺合成活性变化的潜伏期较短，与我们之前报道的锂和吗啡等药物的反应延迟数天至数周形成对比。
The acute administration of d -amphetamine, methamphetamine p -chloroamphetamine, and l -amphetamine reduced the conversion of tryptophan to serotonin (5-HT) in synaptosomes from the rat striatum. d -Amphetamine was approximately twice as potent as l -amphetamine in decreasing conversion activity. In contrast, fenfluramine increased this index of nerve ending 5-HT biosynthesis. None of the amphetamines studied affected synaptosomal uptake of 14C-L-tryptophan when measured in the same tissue preparations in which conversion activity was studied. The activity of solubilized tryptophan hydroxylase in the striatal synaptosomes was decreased by d -amphetamine treatment to the same extent that conversion activity was, accounting for the decrease in conversion activity. Tryptophan hydroxylase activity in the lateral midbrain after d -amphetamine was decreased to the same extent that it was in the nerve ending, but the decrease in the lateral midbrain preceded that observed in the nerve ending. Enzymic activity in the medial midbrain area was unaffected by d -amphetamine. At a concentration of 100 µM none of the amphetamines studied had a demonstrable effect on tryptophan hydroxylase activity in vitro . At 100 µM in vitro and 10 mg/kg in vivo , the two major amphetamine metabolites in the rat, p -hydroxyamphetamine and p -hydroxynorephedrine, failed to influence regional tryptophan hydroxylase activity or synaptosomal conversion of tryptophan to 5-HT. The short latency of the amphetamine-induced changes in nerve ending 5-HT synthetic activity contrasts with the delay of days to weeks in response to such agents as lithium and morphine as we have previously reported.