Marutha Ravindran C R, Ticku Maharaj K
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., 78229-3900, USA.
Brain Res. 2006 May 1;1086(1):35-41. doi: 10.1016/j.brainres.2006.02.106. Epub 2006 Apr 3.
Previous studies from our laboratory revealed that acute ethanol exposure inhibits phosphorylation of mitogen-activated protein (MAP) kinase and extracellular signal-regulated kinases (ERK) in mice. In the present study, we have further investigated effect of chronic administration of ethanol on tyrosine kinase phosphorylation of GABA(A) receptor subunits in the mouse cultured cortical neurons. We observed that there was an up-regulation in tyrosine kinase phosphorylation of the GABA(A) receptor beta(2) and gamma(2) subunits following chronic ethanol exposure, whereas there was no effect on alpha(1) subunit of the GABA(A) receptor in the cultured cortical neurons of mice as determined by Western blotting. These results suggest a potential role for tyrosine kinase phosphorylation of some of the GABA(A) receptor subunits in chronic ethanol-induced tolerance and dependence.
我们实验室之前的研究表明，急性乙醇暴露会抑制小鼠中丝裂原活化蛋白（MAP）激酶和细胞外信号调节激酶（ERK）的磷酸化。在本研究中，我们进一步研究了慢性给予乙醇对小鼠培养皮层神经元中GABA(A)受体亚基酪氨酸激酶磷酸化的影响。我们观察到，慢性乙醇暴露后，GABA(A)受体β(2)和γ(2)亚基的酪氨酸激酶磷酸化上调，而通过蛋白质印迹法测定，在小鼠培养皮层神经元中，GABA(A)受体α(1)亚基未受影响。这些结果表明，某些GABA(A)受体亚基的酪氨酸激酶磷酸化在慢性乙醇诱导的耐受性和依赖性中可能发挥作用。
