title: A Molecular Model for Lithium's Bioactive Form.
abstract: 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 (Kd ∼1.6 mM) compared with other monovalent cations and relevant, considering lithium dosing and physiological concentrations of Mg(2+) 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.
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, National Institute of Standards and Technology, Rockville, Maryland.
authors.forename: Katharine T
authors.initials: KT
authors.lastname: Briggs
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, National Institute of Standards and Technology, Rockville, Maryland.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Giulian
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, Maryland; Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, Maryland.
authors.forename: Gong
authors.initials: G
authors.lastname: Li
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, Maryland; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Joseph P Y
authors.initials: JPY
authors.lastname: Kao
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, National Institute of Standards and Technology, Rockville, Maryland. Electronic address: john.marino@nist.gov.
authors.forename: John P
authors.initials: JP
authors.lastname: Marino
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D008094:Lithium / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular
chemical_list: D000255:Adenosine Triphosphate; D008094:Lithium; D008274:Magnesium