A Molecular Model for Lithium's Bioactive Form

被引：26
作者：
Briggs, Katharine T. [1 ]
Giulian, Gary G. [1 ]
Li, Gong [2 ,3 ]
Kao, Joseph P. Y. [2 ,4 ]
Marino, John P. [1 ]
机构：
[1] Univ Maryland, Inst Biosci & Biotechnol Res, NIST, Rockville, MD 20850 USA
[2] Univ Maryland, Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA
[4] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA
来源：
BIOPHYSICAL JOURNAL | 2016年 / 111卷 / 02期
关键词：
BIPOLAR DISORDER; ATP BINDING; RECEPTORS; COMPETITION; MAGNESIUM; MG2+; ACTIVATION; COMPLEXES; NEURONS; LI+;
D O I：
10.1016/j.bpj.2016.06.015
中图分类号：
Q6 [生物物理学];
学科分类号：
071011 ;
摘要：
Lithium carbonate, a drug for the treatment of bipolar disorder, provides mood stability to mitigate recurrent episodes of mania and/or depression. Despite its long-term and widespread use, the mechanism by which lithium acts to elicit these psychological changes has remained unknown. Using nuclear magnetic resonance (NMR) methods, in this study we characterized the association of lithium with adenosine triphosphate (ATP) and identified a bimetallic (Mg.Li) ATP complex. Lithium's affinity to form this complex was found to be relatively high (K-d similar to 1.6 mM) compared with other monovalent cations and relevant, considering lithium dosing and physiological concentrations of Mg2+ and ATP. The ATP.Mg.Li complex reveals, for the first time, to the best of our knowledge, that lithium can associate with magnesium-bound phosphate sites and then act to modulate purine receptor activity in neuronal cells, suggesting a molecular mode for in vivo lithium action.
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页码：294 / 300
页数：7
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