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乙醇处理及戒断对大鼠神经中间叶阿片促黑激素皮质素原生物合成及加工的影响。

Effects of ethanol treatment and withdrawal on biosynthesis and processing of proopiomelanocortin by the rat neurointermediate lobe.

作者信息

Gianoulakis C, Hutchison W D, Kalant H

机构信息

Department of Psychiatry, McGill University, Verdun, Québec, Canada.

出版信息

Endocrinology. 1988 Mar;122(3):817-25. doi: 10.1210/endo-122-3-817.

DOI:10.1210/endo-122-3-817
PMID:2963739
Abstract

Male Sprague Dawley rats were chronically pair-fed with liquid diets containing 6.5% (vol/vol) ethanol, or equicaloric sucrose. After 21 days the ethanol-containing diet was discontinued and both groups were fed the sucrose diet. Groups of animals were killed on day 22 (0 day of ethanol withdrawal) and 1, 3, 8, and 15 days after ethanol withdrawal and the neurointermediate lobes (NILs) were removed and incubated with [3H]phenylalanine for 3 h. Chronic ethanol treatment induced an increase in the biosynthesis and release of beta-endorphin-like peptides by the rat NIL. After ethanol withdrawal the beta-endorphin-like immunoreactivity content in the NIL and the in vitro release of immunoreactive beta-endorphin (beta EP) by the NIL were significantly lower than in the controls on the first day, whereas no significant difference was found on days 3, 8, and 15 after ethanol withdrawal. The in vitro incorporation of [3H]phenylalanine into POMC, beta-lipotropin and beta EP was found to be higher in the ethanol-treated animals than in the controls on days 0, 1, and 3 after ethanol withdrawal, with no significant difference on days 8 and 15 after ethanol withdrawal. Furthermore, in both the ethanol-treated animals and their pair-fed controls the rate of incorporation of [3H]phenylalanine into total proteins, POMC, beta-lipotropin, and beta EP was significantly higher on days 8 and 15 after ethanol withdrawal than on the day of ethanol withdrawal (day 0), suggesting the implication of a nutritional factor. HPLC analysis of the beta EP peptides indicated that the percentage of acetylated forms of beta EP was higher in the NIL of the alcohol-treated animals, especially on days 8 and 15 after ethanol withdrawal. This observation suggests that though the rates of biosynthesis and release of beta EP-related peptides have returned to normal at 15 days after ethanol treatment, the activity of the enzyme responsible for the acetylation of beta EP remained elevated.

摘要

将雄性斯普拉格-道利大鼠长期成对喂饲含6.5%(体积/体积)乙醇的液体饲料或等热量的蔗糖饲料。21天后,停止喂饲含乙醇的饲料,两组均喂饲蔗糖饲料。在第22天(乙醇戒断0天)以及乙醇戒断后1、3、8和15天处死动物组,取出神经中间叶(NIL),与[3H]苯丙氨酸一起孵育3小时。慢性乙醇处理导致大鼠NIL中β-内啡肽样肽的生物合成和释放增加。乙醇戒断后,NIL中β-内啡肽样免疫反应性含量以及NIL体外释放的免疫反应性β-内啡肽(β-EP)在第一天显著低于对照组,而在乙醇戒断后第3、8和15天未发现显著差异。发现在乙醇戒断后第0、1和3天,乙醇处理的动物中[3H]苯丙氨酸掺入阿黑皮素原、β-促脂素和β-EP的体外掺入率高于对照组,在乙醇戒断后第8和15天无显著差异。此外,在乙醇处理的动物及其成对喂饲的对照组中,乙醇戒断后第8和15天[3H]苯丙氨酸掺入总蛋白、阿黑皮素原、β-促脂素和β-EP的速率显著高于乙醇戒断当天(第0天),提示营养因素的影响。对β-EP肽的HPLC分析表明,乙醇处理动物的NIL中β-EP乙酰化形式的百分比更高,尤其是在乙醇戒断后第8和15天。这一观察结果表明,尽管乙醇处理后15天β-EP相关肽的生物合成和释放速率已恢复正常,但负责β-EP乙酰化的酶的活性仍保持升高。

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