Tyrosine kinase phosphorylation of GABA(A) receptor alpha1, beta2 and gamma2 subunits following chronic intermittent ethanol (CIE) exposure of cultured cortical neurons of mice.
Tyrosine kinase phosphorylation of GABA(A) receptor alpha1, beta2 and gamma2 subunits following chronic intermittent ethanol (CIE) exposure of cultured cortical neurons of mice.
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培养的小鼠皮层神经元慢性间歇性乙醇 (CIE) 暴露后 GABA(A) 受体 α1、β2 和 γ2 亚基的酪氨酸激酶磷酸化。
DOI：
10.1007/s11064-006-9124-9
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发表时间：
2006
影响因子：
4.4
通讯作者：
Ticku,MaharajK
中科院分区：
文献类型：
--
作者：
Ravindran,CRMarutha;Ticku,MaharajK
有证据表明，许多GABAA受体亚基含有酪氨酸激酶的共有序列，磷酸化可能在乙醇调节GABAA受体中起关键作用。近年来，我们研究了慢性乙醇暴露对小鼠皮层神经元酪氨酸激酶磷酸化的影响，发现乙醇暴露可上调GABA A受体β 2和γ 2亚基的酪氨酸激酶磷酸化，而对GABA A受体α 1亚基的酪氨酸激酶磷酸化无影响。本研究采用免疫沉淀和Western blot技术，进一步研究了慢性间歇性乙醇（CIE）对培养的小鼠皮层神经元GABA A受体亚单位（α 1，β 2和γ 2）酪氨酸激酶磷酸化的影响。结果表明，CIE暴露后，GABA A受体β 2和γ 2亚基酪氨酸激酶磷酸化水平明显升高，而α 1亚基则无明显变化。与CE不同的是，这些CIE变化即使在7天后也不会在乙醇停药后恢复到对照水平。急性暴露于乙醇并没有引起GABA A受体亚基的酪氨酸激酶调节的任何变化。总之，与慢性/急性乙醇暴露不同，CIE暴露以持久的方式调节GABA A受体的选择性群体的酪氨酸激酶磷酸化。
There is evidence that many of the GABA A receptor subunits contain consensus sequence for tyrosine kinase, and phosphorylation may play a key role in ethanol’s regulation of GABA A receptors. Recently, we investigated the effect of chronic exposure of ethanol (CE) on tyrosine kinase phosphorylation and reported that there was an up-regulation in tyrosine kinase phosphorylation of the β 2-and γ 2-subunits and no effect on α 1-subunit of the GABA A receptor in the cultured cortical neurons of mice. In the present study, we have further investigated the effect of chronic intermittent administration of ethanol (CIE) on tyrosine kinase phosphorylation of the GABA A receptor subunits (α 1, β 2, and γ 2) in the mouse cultured cortical neurons by immunoprecipitation and Western blot techniques. We observed that there was an up-regulation in the tyrosine kinase phosphorylation of the GABA A receptor β 2-and γ 2-subunits following CIE exposure, and no effect on α 1-subunit in the cultured cortical neurons of mice. These CIE changes, unlike CE, were not reverted back to the control level following ethanol withdrawal even after 7 days. Acute exposure of ethanol did not cause any change in the tyrosine kinase regulation of the GABA A receptor subunits. In conclusion, the CIE exposure, unlike chronic/acute ethanol exposure, regulates the tyrosine kinase phosphorylation of the selective population of GABA A receptors in a long lasting manner.