Regulation of the phosphoinositide cascade by polyamines in brain.
Regulation of the phosphoinositide cascade by polyamines in brain.
复制标题
大脑中多胺对磷酸肌醇级联的调节。
DOI：
10.1046/j.1471-4159.1994.63041319.x
复制
发表时间：
1994
影响因子：
4.7
通讯作者：
Hoss,W
中科院分区：
文献类型：
--
作者：
Periyasamy,S;Kothapalli,MR;Hoss,W
内源性多胺亚精胺和精胺分别增强了鸟苷5′‐O‐（3‐硫代三磷酸）（GTP‐γ‐S）‐刺激的磷酸肌肽转化，ec50值分别为100±30和50±15µM，而合成的多胺esn、N′‐二（3‐氨丙基）‐1,3‐丙二胺和‐乙二胺抑制了GTP‐γ‐S刺激的磷酸肌肽转化。在亚精胺缺失和存在的情况下，GTP‐γ‐S刺激的磷酸肌苷转换的动力学分析表明，GTP‐γ‐S的km没有改变（分别为1,303±270和1,069±214 nM），而vmax增加了206%（分别为1,566±141和4,792±84 cpm），表明亚精胺和GTP‐γ‐S在不同的位点起作用。在没有GTP‐γ‐S的情况下，亚精胺还通过降低磷酸肌肽特异性磷脂酶c的Ca2+需求量来增强Ca2+刺激的磷酸肌肽的转化。NMDA受体复合物上的多胺拮抗剂Arcaine和agmatine并没有阻断亚精胺对GTP‐γ‐S和Ca2+诱导的磷酸肌肽转化的作用，这表明亚精胺的作用不是通过这些特定的多胺位点介导的。此外，亚精胺增加了[3H]磷脂酰肌醇4 -磷酸（EC50= 120±10µM）的水平，但对[3H]磷脂酰肌醇4,5 -二磷酸的水平没有显著影响。综上所述，这些数据表明，在GTP‐γ‐S或Ca2+存在的情况下，亚精胺诱导的磷酸肌苷转换的增强是通过多个水平的磷酸肌苷转换级联介导的。
The endogenous polyamines spermidine and spermine enhanced guanosine 5′‐O‐(3‐thiotriphosphate) (GTP‐γ‐S)‐stimulated phosphoinositide turnover with EC50values of 100 ± 30 and 50 ± 15 µM, respectively, whereas the synthetic polyaminesN,N′‐bis(3‐aminopropyl)‐1,3‐propanediamine and ‐ethylenediamine inhibited GTP‐γ‐S‐stimulated phosphoinositide turnover, with maximal inhibition at 1 mM. Kinetic analysis of GTP‐γ‐S‐stimulated phosphoinositide turnover in the absence and presence of spermidine showed that theKmfor GTP‐γ‐S was not changed (1,303 ± 270 and 1,069 ± 214 nM, respectively), whereas theVmaxwas increased by 206% (1,566 ± 141 and 4,792 ± 84 cpm, respectively), indicating that spermidine and GTP‐γ‐S acted at different sites. Spermidine also enhanced Ca2+‐stimulated phosphoinositide turnover in the absence of GTP‐γ‐S by decreasing the Ca2+requirement of the phosphoinositide‐specific phospholipase C. Arcaine and agmatine, polyamine antagonists at the NMDA receptor complex, did not block the effects of spermidine on GTP‐γ‐S‐ and Ca2+‐induced phosphoinositide turnover, suggesting that the spermidine effects are not mediated through these specific polyamine sites. Furthermore, spermidine increased the level of [3H]phosphatidylinositol 4‐phosphate (EC50= 120 ± 10 µM), without affecting significantly the levels of [3H]phosphatidylinositol and [3H]phosphatidylinositol 4,5‐bisphosphate. Collectively these data indicate that the enhanced phosphoinositide turnover induced by spermidine in the presence of GTP‐γ‐S or Ca2+is mediated through multiple levels of the phosphoinositide turnover cascade.