Hirvonen M R, Savolainen K
National Public Health Institute, Department of Environmental Hygiene and Toxicology, Kuopio, Finland.
Neurochem Res. 1991 Aug;16(8):905-11. doi: 10.1007/BF00965540.
The effects of a single dose of LiCl (2.5 or 10 mEq/kg) on brain inositol and inositol-1-phosphate (Ins1P), intermediates of brain phosphoinositide (PI) turnover, were determined in male Han: Wistar rats. There was a remarkable, 36-58 fold elevation of brain Li+ as the single dose of LiCl was increased 4-fold. Moreover, the accumulation of brain lithium was slow during repeated administration of LiCl. Brain lithium did not correlate with changes in brain PI turnover either after a single or repeated doses. Thus, after a single dose of LiCl the increases in brain Ins1P were much less than the decreases in brain inositol. Also, brain inositol was significantly decreased only with the high dose of LiCl whereas brain Ins1P accumulation was more prominent with the lower dose. Moreover, repeated daily doses of LiCl only transiently increased brain Ins1P at 1 and 7 d whereas inositol remained at control levels throughout the 14 d observation period. Lithium probably caused the transient decrease in brain inositol by inhibiting several enzymes, in addition to the inhibition of myo-inositol mono-phosphates, in the PI cycle. Moreover, a slow dampening down of PI turnover by lithium, possible via an inhibitory action on G-protein-coupling, may also explain the present findings.
在雄性Han:Wistar大鼠中，测定了单剂量氯化锂（2.5或10 mEq/kg）对脑内肌醇和肌醇-1-磷酸（Ins1P）的影响，这两种物质是脑磷酸肌醇（PI）代谢的中间产物。随着单剂量氯化锂增加4倍，脑内锂离子显著升高36 - 58倍。此外，在重复给予氯化锂期间，脑内锂的蓄积缓慢。单次或重复给药后脑内锂含量与脑PI代谢变化均无相关性。因此，单次给予氯化锂后，脑内Ins1P的增加远小于脑内肌醇的减少。而且，仅高剂量氯化锂使脑内肌醇显著降低，而低剂量时脑内Ins1P蓄积更明显。此外，每日重复给予氯化锂仅在第1天和第7天短暂增加脑内Ins1P，而在整个14天观察期内肌醇维持在对照水平。锂可能通过抑制PI循环中的几种酶，除了抑制肌醇单磷酸酶外，导致脑内肌醇短暂减少。此外，锂可能通过对G蛋白偶联的抑制作用，缓慢减弱PI代谢，这也可能解释了目前的研究结果。
