Effects of muscarinic receptor antagonism on the phosphatidylinositol bisphosphate signal transduction pathway after experimental brain injury.
Effects of muscarinic receptor antagonism on the phosphatidylinositol bisphosphate signal transduction pathway after experimental brain injury.
复制标题
实验性脑损伤后毒蕈碱受体拮抗对磷脂酰肌醇二磷酸信号转导通路的影响。
DOI：
10.1016/s0006-8993(96)01002-5
复制
发表时间：
1996
期刊：
影响因子：
2.9
通讯作者：
Prasad,MR
中科院分区：
文献类型：
--
作者：
Lyeth,BG;Gong,QZ;Dhillon,HS;Prasad,MR
测定了大鼠中枢性脑损伤（TBI）后海马组织中磷脂酰肌醇4,5-二磷酸（PIP2）、游离脂肪酸（FFA）和乳酸的含量。损伤后5分钟，从PIP2中提取的脂肪酸减少，表明PIP2减少。在同一时间点，盐水处理的TBI大鼠总游离脂肪酸增加。经盐水处理的TBI大鼠PIP2中花生四烯酸水平显著降低，同时FFA中花生四烯酸和硬脂酸水平升高。TBI后20分钟，pip2衍生脂肪酸或FFA未见明显变化。大鼠损伤后5、20分钟海马乳酸浓度显著升高。一般来说，损伤前给予毒蕈碱拮抗剂东莨菪碱可以减弱这些改变。这些结果表明，中枢液体冲击性脑损伤发生时，海马pip2信号转导通路被激活，磷脂酶c催化pip2的磷酸二酯分解增强是损伤后这些部位立即释放FFA的主要机制。东莨菪碱处理动物的pip2和FFA改变减弱，表明毒蕈碱受体的激活显著促进了TBI中磷脂酶C （PLC）信号转导的病理生理。东莨菪碱处理大鼠乳酸积累的衰减表明，脑外伤诱导的毒蕈碱受体激活也有助于糖酵解代谢和/或离子失衡的增加。
Hippocampal levels of fatty acids extracted from phosphatidylinositol 4,5-bisphosphate (PIP2), free fatty acids (FFA), and lactate were measured after central fluid percussion traumatic brain injury (TBI) in rats. At 5 min after injury, there was a decrease in fatty acids extracted from PIP2suggesting a decrease in PIP2. At the same time point, total FFA increased in saline-treated TBI rats. Levels of arachidonic acid were significantly decreased in PIP2, while at the same time arachidonic and stearic acids increased in FFA in saline-treated TBI rats. No significant alterations in PIP2-derived fatty acids or FFA were observed at 20 min after TBI. Hippocampal concentrations of lactate were significantly elevated at 5 and 20 min after injury in saline-treated rats. In general, these alterations were blunted by preinjury administration of the muscarinic antagonist, scopolamine. These results suggest that the PIP2signal transduction pathway is activated in the hippocampus at the onset of central fluid percussion TBI and that the enhanced phospholipase C-catalyzed phosphodiestric breakdown of PIP2is a major mechanism of liberation of FFA in these sites immediately after such injury. The blunting of PIP2and FFA alterations in animals treated with scopolamine suggests that activation of muscarinic receptors significantly contributes to the phospholipase C (PLC) signal transduction pathophysiology in TBI. The attenuation of lactate accumulation in scopolamine-treated rats suggests that TBI-induced muscarinic receptor activation also contributes to increased glycolytic metabolism and/or ionic imbalances.