Correlated changes in NMDA receptor phosphorylation, functional activity, and sedation by chronic ethanol consumption.
Correlated changes in NMDA receptor phosphorylation, functional activity, and sedation by chronic ethanol consumption.
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DOI：
10.1111/j.1471-4159.2010.06991.x
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发表时间：
2010-12
影响因子：
4.7
通讯作者：
Proctor WR
中科院分区：
文献类型：
--
作者：
Wu PH;Coultrap S;Browning MD;Proctor WR
酒精滥用导致耐受、依赖和记忆损伤，涉及兴奋性谷氨酸能NMDA突触传递。已知NMDA受体经历了活性依赖的适应性功能变化。由于我们观察到酒精对NMDA受体的急性抑制是通过蛋白酪氨酸磷酸化来调节的，所以我们通过慢性乙醇处理来研究蛋白酪氨酸激酶和磷酸酶对NMDA受体功能的影响。我们进行了全细胞记录、Western blotting和行为翻正反射测量，以评估慢性乙醇处理对NMDA受体功能的影响。我们的结果表明，这些受体对慢性酒精摄入后的急性酒精抑制产生了抵抗力。这种耐药的发生没有增加NMDA受体亚单位的表达，但与磷酸化Y-1472 NR2B水平降低、STEP33水平升高、磷酸化p38丝裂原活化蛋白激酶(Pp38MAPK)增加以及对乙醇镇静作用的耐受有关。这些数据表明，NMDA受体亚单位蛋白酪氨酸磷酸化的改变是慢性乙醇摄入导致该受体功能改变的重要原因。因此，保持NMDA受体酪氨酸磷酸化机制的完整性在控制酒精耐受和依赖的进展中可能是重要的。
Alcohol abuse leads to tolerance, dependence and memory impairments that involve excitatory glutamatergic NMDA synaptic transmission. The NMDA receptor is known to undergo activity-dependent adaptive functional changes. Since we observed that acute ethanol inhibition of the NMDA receptor was regulated by protein tyrosine phosphorylation, we investigated the role of protein tyrosine kinases and phosphatases on the NMDA receptor functions by chronic ethanol treatment. We carried out whole-cell recording, Western blotting and behavioral righting reflex measurements to assess the impact of chronic ethanol treatment on NMDA receptor function. Our results indicated that these receptors became resistant to the acute ethanol inhibition following chronic ethanol consumption. This resistance occurred without an increase in the NMDA receptor subunit expression but was associated with decreases in the levels of phospho-Y-1472 NR2B, increases in the levels of STEP33, increases in phospho-p38 mitogen-activated protein kinase (pp38MAPK), and acquisition of tolerance to the sedative effects of ethanol. These data suggested that altered protein tyrosine phosphorylation of the NMDA receptor subunits significantly contributes to functional changes of this receptor by chronic ethanol ingestion. Therefore, preservation of the integrity of tyrosine phosphorylation mechanisms of the NMDA receptor may be important in controlling the progression of alcohol tolerance and dependence.
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影响因子：
3.9
作者：
Hardingham GE
通讯作者：
Hardingham GE
影响因子：
56.9
作者：
Miyakawa, T;Yagi, T;Niki, H
通讯作者：
Niki, H
影响因子：
4.2
作者：
Nagy, J;László, L
通讯作者：
László, L
影响因子：
4.8
作者：
Alvestad, RM;Grosshans, DR;Browning, MD
通讯作者：
Browning, MD
影响因子：
3.3
作者：
Goebel-Goody, S. M.;Davies, K. D.;Browning, M. D.
通讯作者：
Browning, M. D.