Lithium effects on inositol phospholipids and inositol phosphates: evaluation of an in vivo model for assessing polyphosphoinositide turnover in brain.
Lithium effects on inositol phospholipids and inositol phosphates: evaluation of an in vivo model for assessing polyphosphoinositide turnover in brain.
复制标题
锂对肌醇磷脂和肌醇磷酸盐的影响：评估大脑中多磷酸肌醇周转的体内模型的评估。
DOI：
10.1111/j.1471-4159.1992.tb09309.x
复制
发表时间：
1992
影响因子：
4.7
通讯作者：
MacQuarrie,RA
中科院分区：
文献类型：
--
作者：
Sun,GY;Navidi,M;Yoa,FG;Lin,TN;Orth,OE;StubbsJr,EB;MacQuarrie,RA
大鼠脑内注射[~3H]肌醇后，注射氯化锂后，脑组织中标记的肌醇一磷酸水平随时间和剂量的增加而增加。对肌醇磷酸的离子色谱定量分析表明，在注射6mEq/kg氯化锂后4h，肌醇1-磷酸和4-磷酸的质量分别增加了37倍和20倍。尽管幅度较小，但锂还导致脑组织中肌醇1，4-二磷酸水平的增加。锂诱导的标记一磷酸肌醇含量的增加伴随着标记肌醇含量的下降，在注射高剂量的锂(例如10mEq/kg)后，紧随其后的是标记的肌醇磷脂的标记减少。总体而言，注射[~3H]肌醇而不注射锂的动物在甲氨基甲胺或匹罗卡品刺激下对一磷酸肌醇的标记没有明显差异。然而，当动物注射[~3H]肌醇，然后再注射锂时，在注射这些化合物时标记的肌醇一磷酸的水平有很大的增加。给服用锂的小鼠注射阿托品，可以部分减少由于单独服用锂而累积的标记肌醇一磷酸的量。此外，阿托品还能阻断匹罗卡品引起的标记一磷酸肌醇水平的升高。这些结果表明，放射性示踪技术与锂离子注入相结合，可用于评估药物和受体激动剂对涉及脑内多磷肌醇代谢的信号系统的影响。
Administration of lithium chloride to rats injected intracerebrally with [3H]inositol led to time‐ and dose‐dependent increases in levels of labeled inositol monophosphates in brain. Quantitative analysis of the inositol phosphates by ion chromatography revealed 37‐ and 20‐fold increases in the mass ofmyo‐inositol 1‐phosphate and 4‐phosphate, respectively, at 4 h intraperitoneal after injections of 6 mEq/kg of lithium chloride. Albeit to a much lesser extent, lithium administration also resulted in an increase in the level ofmyo‐inositol 1,4‐bisphosphate in brain. The lithium‐induced increase in content of labeled inositol monophosphates was marked by a concomitant decrease in content of labeled inositol, and after injections of high doses of lithium, e.g., 10 mEq/kg, this was followed by a general decrease in labeling of the inositol phospholipids. In general, animals injected with [3H]inositol but not lithium did not reveal obvious differences in labeling of inositol monophosphates on stimulation by mecamylamine or pilocarpine. However, when animals were injected with [3H]inositol and then lithium, there were large increases in the levels of labeled inositol monophosphates on administration of these compounds. Administration of atropine to the lithium‐treated mice led to a partial reduction in the amount of labeled inositol monophosphates accumulated due to the administration of lithium alone. Furthermore, atropine was able to block the pilocarpine‐induced increase in level of labeled inositol monophosphates. These results demonstrate the suitable use of the radiotracer technique together with lithium administration for assessing the effects of drugs and receptor agonists on the signaling system involving polyphosphoinositide turnover in brain.