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糖皮质激素代谢产物和神经甾体对γ-氨基丁酸-A受体的快速非基因组效应。

Rapid non-genomic effect of glucocorticoid metabolites and neurosteroids on the gamma-aminobutyric acid-A receptor.

作者信息

Strömberg J, Bäckström T, Lundgren P

机构信息

Umeå Neurosteroid Research Center, Obstetrics & Gynecology, Department of Clinical Science, Building 5B Level 5, Umeå University, Norrland University Hospital, Umeå, Sweden SE 901 85.

出版信息

Eur J Neurosci. 2005 Apr;21(8):2083-8. doi: 10.1111/j.1460-9568.2005.04047.x.

DOI:10.1111/j.1460-9568.2005.04047.x
PMID:15869504
Abstract

Glucocorticoids and neurosteroids, such as allopregnanolone and tetrahydrodeoxycorticosterone, are released during stress. A non-genomic effect of glucocorticoids has been established but is not yet fully understood. We have studied the effect of glucocorticoid metabolites on the gamma-aminobutyric acid (GABA) system. In these experiments we studied the effects of the glucocorticoid metabolites allotetrahydrocortisol, tetrahydrocortisol, allotetrahydrocortisone and tetrahydrocortisone in rat cortical microsacs. Our results showed that both these cortisol and cortisone metabolites reduce GABA-mediated chloride ion uptake. This reduction was not observed in the presence of allopregnanolone but allotetrahydrocortisol interacts with allopregnanolone, enhancing the allopregnanolone-stimulated potentiation of GABA-mediated chloride ion uptake. This enhanced effect was completely blocked by the addition of 30 microm of the 3beta-isomer of allopregnanolone, isoallopregnanolone. Our findings show that steroids released during stress interact with each other and GABA in the GABA system.

摘要

糖皮质激素和神经甾体,如别孕烯醇酮和四氢脱氧皮质酮,在应激过程中释放。糖皮质激素的非基因组效应已得到证实,但尚未完全了解。我们研究了糖皮质激素代谢产物对γ-氨基丁酸(GABA)系统的影响。在这些实验中,我们研究了糖皮质激素代谢产物别四氢皮质醇、四氢皮质醇、别四氢可的松和四氢可的松对大鼠皮质微囊的影响。我们的结果表明,这些皮质醇和可的松代谢产物均会降低GABA介导的氯离子摄取。在别孕烯醇酮存在的情况下未观察到这种降低,但别四氢皮质醇与别孕烯醇酮相互作用,增强了别孕烯醇酮刺激的GABA介导的氯离子摄取增强作用。添加30微摩尔的别孕烯醇酮3β-异构体异别孕烯醇酮可完全阻断这种增强作用。我们的研究结果表明,应激过程中释放的甾体在GABA系统中彼此相互作用并与GABA相互作用。

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