Regulation of α3-containing GABAA receptors in guinea-pig adrenal medullary cells by adrenal steroids.

Regulation of α3-containing GABAA receptors in guinea-pig adrenal medullary cells by adrenal steroids.
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肾上腺类固醇对豚鼠肾上腺髓质细胞中含α3 GABAA 受体的调节。

DOI:
10.1016/j.neuroscience.2013.08.046
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发表时间:
2013
期刊:
影响因子:
3.3
通讯作者:
Matsuoka H
Matsuoka H
中科院分区:
医学3区
文献类型:
--
作者:
Inoue M;Harada K;Nakamura J;Matsuoka H

文献摘要

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GABA被认为是肾上腺髓质(AM)细胞中的旁分泌因子。因此,我们的电生理学和免疫学研究的特性GABAAR(GABAARs)在豚鼠AM细胞。GABA在水浴中产生一个电压为−60 mV的内向电流,且呈剂量依赖性,EC 50为32.3 μM。0.01 μM及以上浓度的别孕烯醇酮可增强GABA诱导的电流。预先暴露于别孕烯醇酮导致GABA激活GABAAR的EC 50降低。Zn ~(2+)呈剂量依赖性地抑制GABA诱导的电流,IC_(50)为18 μM,而La ~(3+)则增强GABA诱导的电流。苯二氮卓类类似物地西泮增强GABA电流的效力是唑吡坦的3倍,L-838,417也增强了该电流,但对含α1的GABAAR无作用。免疫组化检测到GABAAR α3亚基,而非α1和γ2亚基。糖皮质激素活性可促进PC 12细胞α3亚基的表达。结果表明,豚鼠AM细胞GABAARs主要由α3、β和γ2亚基组成,并可被别孕酮增强,糖皮质激素可能在α3亚基的表达中起主要作用。
GABA is thought to function as a paracrine factor in adrenal medullary (AM) cells. Thus, we electrophysiologically and immunologically examined the properties of GABAAreceptors (GABAARs) in guinea-pig AM cells. Bath application of GABA produced an inward current at −60 mV in a dose-dependent manner with an EC50of 32.3 μM. This GABA-induced current was enhanced by allopregnanolone at concentrations of 0.01 μM and more. A prior exposure to allopregnanolone resulted in a decrease in an EC50for GABA in activating GABAARs. The GABA-induced current was suppressed by Zn2+in a dose-dependent manner with an IC50of 18 μM, whereas it was enhanced by 100 μM La3+. The benzodiazepine analog diazepam was three times more potent than zolpidem in enhancing the GABA current, and it was also augmented by L-838,417, which has no action on α1-containing GABAARs. The GABAAR α3, but not α1, and γ2 subunits were immunologically detected at the cell periphery. The expression of α3 subunits in PC12 cells was enhanced by glucocorticoid activity. The results indicated that GABAARs in guinea-pig AM cells mainly comprise α3, β, and γ2 subunits and are enhanced by allopreganalone and glucocorticoids may play a major role in the expression of α3 subunits.