治疗浓度的锂可抑制人红细胞中的肌醇-1-磷酸酶。

Inositol-1-phosphatase of human erythrocytes is inhibited by therapeutic lithium concentrations.

作者信息

Agam G, Livne A

机构信息

Ben Gurion University of the Negev, Beer Sheva, Israel.

出版信息

Psychiatry Res. 1989 Feb;27(2):217-24. doi: 10.1016/0165-1781(89)90137-6.

DOI:10.1016/0165-1781(89)90137-6

PMID:2540502

Abstract

Lithium is widely used in psychiatric chemotherapy and is especially effective in the treatment of manic-depressive illness (MDI), but the mechanism for its therapeutic properties and side effects remains to be elucidated. One of the possibilities relates to the inhibitory effect of Li+ on inositol-1-phosphatase (I-1-P'ase) activity. Indeed, the concentration of inositol-1-phosphate (I-1-P) after treatment with Li+ was shown to be increased in various mammalian cells. Yet, no direct study of I-1-P'ase activity in human cells has been reported. Erythrocytes are readily accessible for routine studies and could facilitate the investigation of I-1-P'ase as affected by Li+ in relation to MDI. It is now shown that I-1-P'ase can be measured in lysate of human erythrocytes, using a small blood sample. The enzymatic activity is localized in the soluble fraction. The Km for I-1-P is 0.14 mM. Intriguingly, the Ki for Li+ is 0.86 mM, within the range of therapeutic concentrations in MDI patients.

摘要

锂广泛应用于精神科化学治疗，尤其在治疗躁郁症（MDI）方面效果显著，但其治疗特性及副作用的机制仍有待阐明。一种可能性与Li⁺对肌醇-1-磷酸酶（I-1-P'ase）活性的抑制作用有关。事实上，在用Li⁺处理后，多种哺乳动物细胞中肌醇-1-磷酸（I-1-P）的浓度显示会升高。然而，尚未有关于人类细胞中I-1-P'ase活性的直接研究报道。红细胞易于获取，可用于常规研究，有助于研究Li⁺对I-1-P'ase的影响以及与MDI的关系。现已表明，使用少量血液样本，可在人红细胞裂解物中检测I-1-P'ase。酶活性定位于可溶性部分。I-1-P的Km为0.14 mM。有趣的是，Li⁺的Ki为0.86 mM，处于MDI患者治疗浓度范围内。