Role of inositol-1-phosphatase inhibition in the mechanism of action of lithium.
Role of inositol-1-phosphatase inhibition in the mechanism of action of lithium.
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DOI：
10.1111/j.1600-0773.1990.tb02075.x
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发表时间：
1990-03
期刊：
影响因子：
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通讯作者：
R. Belmaker;A. Livne;G. Agam;Moscovich Dg;N. Grisaru;G. Schreiber;S. Avissar;Abraham Danon;O. Kofman
中科院分区：
文献类型：
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作者：
R. Belmaker;A. Livne;G. Agam;Moscovich Dg;N. Grisaru;G. Schreiber;S. Avissar;Abraham Danon;O. Kofman
Li对去甲肾上腺素能腺苷酸环化酶的抑制可能是由于Li抑制了激动剂诱导的GTP与g蛋白结合的增加。Li对g蛋白功能的抑制可能影响磷脂酰肌醇介导的第二信使系统以及环amp介导的系统。但Sherman、Berridge等人提出Li通过抑制肌醇-1磷酸酶影响磷脂酰肌醇代谢。我们最近已经能够测量人体红细胞中的肌醇-1-磷酸酶。与对照组相比，接受Li治疗的患者的初步数据表明，在接受Li治疗的患者体内，这种酶确实受到抑制。然而，在Li治疗中加入肌醇的一系列大鼠实验并没有发现肌醇可以逆转Li的作用。慢性口服大剂量肌醇不能逆转锂诱导的多尿（以烦渴来测量）、锂诱导的体重减轻或锂诱导的探索性行为抑郁。这些结果表明Li对肌醇-1磷酸酶的抑制确实存在于体内。然而，肌醇-1-磷酸酶抑制的生理意义尚未确定。
Li inhibition of noradrenergic adenylate cyclase may be due to inhibition by Li of agonist-induced increases in GTP binding to G-protein. Such inhibition by Li of G-protein function could have effects on phosphatidyl-inositol-mediated second messenger systems as well as on cyclic AMP-mediated systems. However, Sherman, Berridge and others have proposed that Li affects phosphatidylinositol metabolism by inhibiting inositol-1-phosphatase. We recently have been able to measure inositol-1-phosphatase in human red blood cells. Preliminary data on patients treated with Li compared with controls suggests that the enzyme is indeed inhibited in vivo in patients undergoing Li treatment. However, a series of experiments in rats on addition of inositol to Li treatment did not find that inositol could reverse Li effects. Chronic oral high dose inositol does not reverse Li-induced polyuria (measured by polydipsia), Li-induced weight loss or Li-induced depression of exploratory behavior. These results suggest that Li inhibition of inositol-1-phosphatase indeed occurs in vivo. However, the physiological significance of inositol-1-phosphatase inhibition is not yet established.