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氟西泮耐受大鼠脑内γ-氨基丁酸A型/苯二氮䓬受体β亚基mRNA表达降低。

Decreased expression of gamma-aminobutyric acid type A/benzodiazepine receptor beta subunit mRNAs in brain of flurazepam-tolerant rats.

作者信息

Zhao T J, Chiu T H, Rosenberg H C

机构信息

Department of Pharmacology, Medical College of Ohio, Toledo 43699, USA.

出版信息

J Mol Neurosci. 1994 Fall;5(3):181-92. doi: 10.1007/BF02736732.

DOI:10.1007/BF02736732
PMID:7654520
Abstract

The expression of GABAA/benzodiazepine beta subunit mRNAs was studied in cerebral cortex, hippocampus, and cerebellum of flurazepam-treated rats. Immediately following 4 wk of treatment, beta 2 and beta 3 subunit mRNAs were significantly reduced in cerebellum and hippocampus, whereas only beta 2 was decreased in cortex. These decreases had largely reversed 48 h following flurazepam treatment. After 2 wk of treatment, both beta 2 and beta 3 mRNAs were reduced in cerebellum, and beta 3 mRNA was reduced in hippocampus, but neither was changed in cortex. Four hours after an acute flurazepam treatment, the only change was a decrease in beta 3 mRNA in hippocampus. These results indicate that the expression of GABAA receptor beta subunit mRNAs in different brain regions is differentially regulated during chronic flurazepam treatment, and some changes occur within hours after a single large dose.

摘要

在接受氟西泮治疗的大鼠的大脑皮层、海马体和小脑中研究了GABAA/苯二氮䓬β亚基mRNA的表达。在治疗4周后立即检测发现,小脑和海马体中的β2和β3亚基mRNA显著减少,而皮层中只有β2减少。在氟西泮治疗48小时后,这些减少大多逆转。治疗2周后,小脑中β2和β3 mRNA均减少,海马体中β3 mRNA减少,但皮层中两者均未改变。急性氟西泮治疗4小时后,唯一的变化是海马体中β3 mRNA减少。这些结果表明,在慢性氟西泮治疗期间,不同脑区的GABAA受体β亚基mRNA的表达受到不同的调节,并且在单次大剂量给药后的数小时内会发生一些变化。

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Decreased expression of gamma-aminobutyric acid type A/benzodiazepine receptor beta subunit mRNAs in brain of flurazepam-tolerant rats.氟西泮耐受大鼠脑内γ-氨基丁酸A型/苯二氮䓬受体β亚基mRNA表达降低。
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引用本文的文献

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Silent GABAA synapses during flurazepam withdrawal are region-specific in the hippocampal formation.氟西泮戒断期间沉默的GABAA突触在海马结构中具有区域特异性。
J Neurosci. 1997 May 15;17(10):3467-75. doi: 10.1523/JNEUROSCI.17-10-03467.1997.
2
Molecular mechanisms of benzodiazepine-induced down-regulation of GABAA receptor alpha 1 subunit protein in rat cerebellar granule cells.苯二氮䓬类药物诱导大鼠小脑颗粒细胞中GABAA受体α1亚基蛋白下调的分子机制
Br J Pharmacol. 1996 Jul;118(5):1103-10. doi: 10.1111/j.1476-5381.1996.tb15512.x.

本文引用的文献

1
Levels of GABAa receptor subunit mRNA in rat brain following flurazepam treatment.氟西泮处理后大鼠脑中 GABAa 受体亚单位 mRNA 的水平。
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Differential effects of chronic ethanol administration on GABA(A) receptor alpha1 and alpha6 subunit mRNA levels in rat cerebellum.慢性乙醇给药对大鼠小脑 GABA(A) 受体 α1 和 α6 亚基 mRNA 水平的差异影响。
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Differential effects on GABAA receptor gamma 2-subunit messenger RNA by tolerance to and withdrawal from pentobarbital--an in situ hybridization study.
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Tolerance to the effects of diazepam, clonazepam and bretazenil on GABA-stimulated Cl- influx in flurazepam tolerant rats.氟西泮耐受大鼠对安定、氯硝西泮和溴替唑仑作用于γ-氨基丁酸(GABA)刺激的氯离子内流的耐受性。
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Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors.β亚基在决定人类γ-氨基丁酸A型受体药理学特性中的作用。
Mol Pharmacol. 1993 Dec;44(6):1211-8.
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Improved proteinase K digestion for the rapid isolation of mRNA from mammalian tissues.改进蛋白酶K消化法用于从哺乳动物组织中快速分离mRNA
Biotechniques. 1993 Oct;15(4):620, 622, 624-6.
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Molecular heterogeneity of the type I GABAA/benzodiazepine receptor complex.I型γ-氨基丁酸A/苯二氮䓬受体复合物的分子异质性。
Eur J Pharmacol. 1994 Mar 15;267(1):123-8. doi: 10.1016/0922-4106(94)90233-x.
8
Reduced expression of gamma-aminobutyric acid type A/benzodiazepine receptor gamma 2 and alpha 5 subunit mRNAs in brain regions of flurazepam-treated rats.氟西泮处理大鼠脑区中γ-氨基丁酸A型/苯二氮䓬受体γ2和α5亚基mRNA表达降低。
Mol Pharmacol. 1994 Apr;45(4):657-63.
9
Regional changes in [3H]zolpidem binding to brain benzodiazepine receptors in flurazepam tolerant rat: comparison with changes in [3H]flunitrazepam binding.氟西泮耐受大鼠脑内苯二氮䓬受体与[³H]唑吡坦结合的区域变化:与[³H]氟硝西泮结合变化的比较
J Pharmacol Exp Ther. 1994 Feb;268(2):675-82.
10
Chronic ethanol treatment upregulates the GABA receptor beta subunit expression.
Brain Res Mol Brain Res. 1994 May;23(3):246-52. doi: 10.1016/0169-328x(94)90231-3.