Haleem D J
Department of Biochemistry, University of Karachi, Pakistan.
Life Sci. 1990;47(11):971-9. doi: 10.1016/0024-3205(90)90544-2.
In previous studies, long term treatment with ethanol has been shown to enhance brain 5-hydroxytryptamine 5-(HT) metabolism by increasing the activity of the regulatory enzyme tryptophan hydroxylase and or availability of circulating tryptophan secondarily to an inhibition of hepatic tryptophan pyrrolase. In the present study ethanol treatment given for two weeks decreased hepatic apo-tryptophan pyrrolase but not total tryptophan pyrrolase activity in rats. Tryptophan levels in plasma and brain did not increase significantly. But there was a marked increase of 5-HT but not 5-hydroxyindoleacetic acid (5-HIAA) concentration in brain, suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in controls and ethanol treated rats. One hour after tryptophan injection (50 mg/kg i.p.) plasma concentrations of total and free tryptophan were identical in controls and ethanol treated rats, but the increases of brain tryptophan 5-HT and 5-HIAA were considerably greater in the latter group. The results are consistent with long term ethanol treatment enhancing brain serotonin metabolism and show that brain uptake/utilization of exogenous tryptophan is increased in ethanol treated rats and may be useful to understand the role and possible mechanism of tryptophan/serotonin involvement in mood regulation.
在先前的研究中,已表明长期用乙醇治疗可通过增加调节酶色氨酸羟化酶的活性和/或循环色氨酸的可用性(继发于对肝色氨酸吡咯酶的抑制)来增强脑5-羟色胺(5-HT)代谢。在本研究中,对大鼠给予两周的乙醇治疗可降低肝脱辅基色氨酸吡咯酶,但不降低总色氨酸吡咯酶活性。血浆和脑中的色氨酸水平没有显著增加。但是脑中5-HT浓度显著增加,而5-羟吲哚乙酸(5-HIAA)浓度没有增加,这表明色氨酸羟化酶的活性可能增加。因此,比较了对照组和乙醇处理组大鼠色氨酸负荷对脑5-HT代谢的影响。色氨酸注射(50mg/kg腹腔注射)1小时后,对照组和乙醇处理组大鼠血浆中总色氨酸和游离色氨酸浓度相同,但后一组脑中色氨酸、5-HT和5-HIAA的增加幅度更大。这些结果与长期乙醇治疗增强脑血清素代谢一致,并表明乙醇处理组大鼠脑中对外源性色氨酸的摄取/利用增加,这可能有助于理解色氨酸/血清素在情绪调节中的作用和可能机制。