SEROTONIN DEFICIENCY IN EXPERIMENTAL HYPERPHENYLALANINEMIA
SEROTONIN DEFICIENCY IN EXPERIMENTAL HYPERPHENYLALANINEMIA
复制标题
DOI：
10.1111/j.1471-4159.1974.tb06928.x
复制
发表时间：
1974-01-01
影响因子：
4.7
通讯作者：
LOO, YH
中科院分区：
文献类型：
--
作者：
LOO, YH
在断奶前大鼠中研究了5-羟色胺耗竭的机制，其中通过注射p-CPA和l-PA诱导了苯丙酮尿症的化学模拟。选择实验条件以有效地最小化色氨酸羟基化不足和5-HTP转运的贡献。高苯丙氨酸血症大脑中5-HT的过度降解可能是一种可能的机制。在5-HTP负荷前和负荷后1小时，在有和没有帕吉林预处理的情况下，观察到的脑5-HTP、5-HT、5-HIAA水平清楚地表明，在高苯丙氨酸血症动物中，5-HT的体内合成大大减少。这种合成缺陷在很大程度上可以通过在全脑的高速可溶性上清液提取物中测量的芳香族氨基酸脱羧酶活性降低来解释。在高苯丙氨酸血症动物中也观察到全脑颗粒亚细胞部分中5-HT的储存减少。显着降低结合血清素在大脑中的水平发生与PEA注射到正常动物。
The mechanism of serotonin depletion was studied in the preweanling rat in which a chemical simulation of phenylketonuria had been induced by injections of p‐CPA andl‐PA. Experimental conditions were selected to effectively minimize the contribution by deficient tryptophan hydroxylation and 5‐HTP transport. Excessive degradation of 5‐HT in the hyperphenylalaninemic brain could be eliminated as a possible mechanism. The observed levels of cerebral 5‐HTP, 5‐HT, 5‐HIAA before and 1 h after 5‐HTP loading, with and without pargyline pretreatment, clearly demonstrate greatly diminishedin vivosynthesis of 5‐HT in the hyperphenylalaninemic animal. This deficient synthesis could largely be accounted for by decreased activity of aromaticl‐amino acid decarboxylase measured in the high speed soluble supernatant extracts of whole brain. Decreased storage of 5‐HT in the particulate subcellular fraction of whole brain was also noted in the hyperphenylalaninemic animal. Significant lowering of bound serotonin levels in the brain occurred with injections of PEA into normal animals.