The effects of lithium on platelet phosphoinositide metabolism.
The effects of lithium on platelet phosphoinositide metabolism.
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锂对血小板磷酸肌醇代谢的影响。
DOI：
10.1042/bj2360895
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Detwiler,TC
中科院分区：
文献类型：
--
作者：
Huang,EM;Detwiler,TC
本文研究了用10 mM-Li+预孵育血小板90 min对磷脂酰肌醇代谢的影响。测量了[32 P]磷酸标记的磷酸肌醇和[3 H]肌醇标记的肌醇单磷酸、二磷酸和三磷酸（InsP、InsP 2和InsP 3）。Li+对InsP、InsP 2和InsP 3的基础放射性无影响，但使InsP的基础放射性增加1.8倍。Li+使凝血酶诱导的InsP、InsP 2和InsP 3的标记积累分别增加4、3和2倍。尽管InsP 2和InsP 3的标记升高在30-60分钟内恢复到接近基础值，但在向Li+处理的血小板中加入凝血酶后60分钟内InsP的高标记并未下降，这与Li+对InsP磷酸酶的抑制一致。Li+的影响不是由于凝血酶剂量-反应关系的转变;凝血酶浓度的增加提高了放射性标记的肌醇磷酸的初始生产率，而Li+影响了二次生产或其去除率。Li+对磷酸肌醇代谢的唯一影响是凝血酶诱导的Li+处理血小板中标记的磷脂酰肌醇4-磷酸的减少（P <0.05）;这表明对磷脂酶C有影响。Li+增强（P <0.05）凝血酶诱导的标记溶血磷脂酰肌醇的增加，表明对磷脂酶A2的影响。结论：Li+抑制InsP磷酸酶，并对活化血小板的磷酸肌醇代谢有其它影响。观察到的效果发生太慢，是Li+增强激动剂诱导的血小板活化的机制。
The effects on phosphoinositide metabolism of preincubation of platelets for 90 min with 10 mM-Li+ were studied. Measurements were made of [32P]phosphate-labelled phosphoinositides and of [3H]inositol-labelled inositol mono-, bis- and tris-phosphate (InsP, InsP2 and InsP3). Li+ had no effect on the basal radioactivity in the phosphoinositides or in InsP2 or InsP3, but it caused a 1.8-fold increase in the basal radioactivity in InsP. Li+ caused a 4-, 3- and 2-fold enhanced thrombin-induced accumulation of label in InsP, InsP2 and InsP3 respectively. Although the elevated labelling of InsP2 and InsP3 returned to near-basal values within 30-60 min, the high labelling of InsP did not decline over a period of 60 min after addition of thrombin to Li+-treated platelets, consistent with inhibition of InsP phosphatase by Li+. The effect of Li+ was not due to a shift in the thrombin dose-response relationship; increasing concentrations of thrombin enhanced the initial rate of production of radiolabelled inositol phosphates, whereas Li+ affected either a secondary production or the rate of their removal. The only observed effect of Li+ on phosphoinositide metabolism was a thrombin-induced decrease (P less than 0.05) in labelled phosphatidylinositol 4-phosphate in Li+-treated platelets; this suggests an effect on phospholipase C. Li+ enhanced (P less than 0.05) the thrombin-induced increase in labelled lysophosphatidylinositol, suggesting an effect on phospholipase A2. It is concluded that Li+ inhibits InsP phosphatase and has other effects on phosphoinositide metabolism in activated platelets. The observed effects occur too slowly to be the mechanism by which Li+ potentiates agonist-induced platelet activation.