Batty I, Nahorski S R
Department of Pharmacology and Therapeutics, University of Leicester, U.K.
Biochem J. 1987 Nov 1;247(3):797-800. doi: 10.1042/bj2470797.
The effects of Li+ on carbachol-stimulated phosphoinositide metabolism were examined in rat cerebral-cortex slices labelled with myo-[2-3H]inositol. The muscarinic agonist carbachol evoked an enhanced steady-state accumulation of [3H]inositol monophosphate ([3H]InsP1), [3H]inositol bisphosphate ([3H]InsP2), [3H]inositol 1,3,4-trisphosphate ([3H]Ins(1,3,4)P3), [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) and [3H]inositol tetrakisphosphate ([3H]InsP4). Li+ (5 mM), after a 10 min lag, severely attenuated carbachol-stimulated [3H]InsP4 accumulation while simultaneously potentiating accumulation of both [3H]InsP1 and [3H]InsP2 and, at least initially, of [3H]Ins(1,3,4)P3. These data are consistent with inhibition of inositol mono-, bis- and 1,3,4-tris-phosphate phosphatases to different degrees by Li+ in brain, but are not considered to be completely accounted for in this way. Potential direct and indirect mechanisms of the inhibitory action of Li+ on [3H]InsP4 accumulation are considered. The present results stress the complex action of Li+ on cerebral inositol metabolism and indicate that more complex mechanisms than are yet evident may regulate this process.
在以肌醇-[2-³H]标记的大鼠大脑皮层切片中，研究了锂离子对卡巴胆碱刺激的磷酸肌醇代谢的影响。毒蕈碱激动剂卡巴胆碱引起[³H]肌醇单磷酸（[³H]InsP1）、[³H]肌醇双磷酸（[³H]InsP2）、[³H]肌醇1,3,4-三磷酸（[³H]Ins(1,3,4)P3）、[³H]肌醇1,4,5-三磷酸（[³H]Ins(1,4,5)P3）和[³H]肌醇四磷酸（[³H]InsP4）的稳态积累增强。锂离子（5 mM）在延迟10分钟后，严重减弱了卡巴胆碱刺激的[³H]InsP4积累，同时增强了[³H]InsP1和[³H]InsP2的积累，并且至少在最初增强了[³H]Ins(1,3,4)P3的积累。这些数据与锂离子在脑中不同程度地抑制肌醇单磷酸酶、双磷酸酶和1,3,4-三磷酸酶一致，但认为不能完全用这种方式解释。考虑了锂离子对[³H]InsP4积累抑制作用的潜在直接和间接机制。目前的结果强调了锂离子对脑肌醇代谢的复杂作用，并表明可能有比目前明显的更为复杂的机制来调节这一过程。
