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Tyrosine Kinase Phosphorylation of GABAA Receptor α1, β2 and γ2 Subunits Following Chronic Intermittent Ethanol (CIE) Exposure of Cultured Cortical Neurons of Mice

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Abstract

There is evidence that many of the GABAA receptor subunits contain consensus sequence for tyrosine kinase, and phosphorylation may play a key role in ethanol’s regulation of GABAA 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 β2- and γ2- subunits and no effect on α1-subunit of the GABAA 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 GABAA receptor subunits (α1, β2, and γ2) 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 GABAA receptor β2- and γ2-subunits following CIE exposure, and no effect on α1-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 GABAA receptor subunits. In conclusion, the CIE exposure, unlike chronic/acute ethanol exposure, regulates the tyrosine kinase phosphorylation of the selective population of GABAA receptors in a long lasting manner.

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Acknowledgments

We thank Dr. A.K. Mehta for his excellent help. This work was supported by funds from National Institute of Alcohol Abuse & Alcoholism Grant# AA10552.

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Correspondence to Maharaj K. Ticku.

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Ravindran, C.M., Ticku, M.K. Tyrosine Kinase Phosphorylation of GABAA Receptor α1, β2 and γ2 Subunits Following Chronic Intermittent Ethanol (CIE) Exposure of Cultured Cortical Neurons of Mice. Neurochem Res 31, 1111–1118 (2006). https://doi.org/10.1007/s11064-006-9124-9

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