Pandey S C
Department of Psychiatry, College of Medicine, University of Illinois at Chicago, USA.
J Neurochem. 1996 Dec;67(6):2355-61. doi: 10.1046/j.1471-4159.1996.67062355.x.
The goal of this investigation was to examine whether postreceptor sites [Gq/11 protein and phospholipase C (PLC) isozymes] of the phosphoinositide signal transduction system are involved in neuroadaptational mechanisms in the brain during chronic ethanol consumption. It was observed that acute ethanol treatment has no effect on the immunolabeling of PLC-beta 1, -gamma 1, and -delta 1 and the alpha subunit of Gq/11 protein in the rat cortex as determined by western blotting using specific monoclonal antibodies. On the other hand, chronic ethanol consumption (15 days) resulted in a significant decrease in the immunolabeling of PLC-beta 1, whereas under identical conditions, the immunolabeling of PLC-gamma 1 and -delta 1 isozymes was not significantly altered. The decreased immunolabeling of PLC-beta 1 during chronic ethanol consumption was not altered by 24 h of withdrawal after 15 days of ethanol consumption. The immunolabeling of the alpha subunit of Gq/11 protein was significantly decreased after 15 days of ethanol consumption but had returned to normal levels after 24 h of ethanol withdrawal. Also, chronic ethanol treatment resulted in a significant decrease in phosphatidylinositol 4,5-bisphosphate-specific PLC activity, which remained the same after 24 h of ethanol withdrawal. These results suggest that decreased PLC activity during ethanol consumption and its withdrawal may be due to decreased protein levels of the Gq/11 protein-coupled PLC-beta 1 isozyme but not the PLC-gamma 1 or -delta 1 isozyme in the rat cortex. It is possible that changes in the protein levels of the Gq/11 protein-coupled PLC-beta 1 isozyme and in PLC activity in the brain may be involved in the cellular adaptation to chronic ethanol exposure.
本研究的目的是探讨磷酸肌醇信号转导系统的受体后位点（Gq/11蛋白和磷脂酶C（PLC）同工酶）是否参与慢性乙醇摄入期间大脑中的神经适应性机制。通过使用特异性单克隆抗体的蛋白质印迹法测定，观察到急性乙醇处理对大鼠皮层中PLC-β1、-γ1和-δ1以及Gq/11蛋白的α亚基的免疫标记没有影响。另一方面，慢性乙醇摄入（15天）导致PLC-β1的免疫标记显著降低，而在相同条件下，PLC-γ1和-δ1同工酶的免疫标记没有显著改变。在乙醇摄入15天后，慢性乙醇摄入期间PLC-β1免疫标记的降低在24小时戒断后没有改变。乙醇摄入15天后，Gq/11蛋白α亚基的免疫标记显著降低，但在乙醇戒断24小时后恢复到正常水平。此外，慢性乙醇处理导致磷脂酰肌醇4,5-二磷酸特异性PLC活性显著降低，在乙醇戒断24小时后保持不变。这些结果表明，乙醇摄入及其戒断期间PLC活性降低可能是由于大鼠皮层中Gq/11蛋白偶联的PLC-β1同工酶的蛋白水平降低，而不是PLC-γ1或-δ1同工酶。大脑中Gq/11蛋白偶联的PLC-β1同工酶的蛋白水平变化和PLC活性变化可能参与细胞对慢性乙醇暴露的适应。
