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Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels

The Pharmacogenomics Journal volume 4, pages 365–373 (2004)Cite this article

ABSTRACT

Chronic lithium treatment of B-lymphoblast cell lines (BLCLs) from bipolar-I disorder (BD-I) patients and healthy subjects ex vivo attenuates agonist- and thapsigargin-stimulated intracellular calcium (Ca2+) responses. As these findings suggest that chronic lithium treatment modifies receptor (ROCE) and/or store-operated Ca2+ entry (SOCE) mechanisms, we determined whether chronic lithium treatment of BLCLs modified the expression of two members of the transient receptor potential channels (TRPC1 & 3), which participate in ROCE/SOCE. Chronic lithium treatment significantly reduced BLCL TRPC3 immunoreactivity (repeated-measures ANOVA, P=0.00005), with interaction effects of diagnosis (P=0.037) and sex (P=0.040). The lithium-induced decrease was greatest in BLCLs from female BD-I patients compared with those from healthy females (−27%) and with vehicle-treated BLCLs from female BD-I patients (−33%). However, lithium treatment did not affect TRPC1 and 3 mRNA levels, and TRPC1 immunoreactivity. Downregulation of TRPC3 may be an important mechanism by which lithium ameliorates pathophysiological Ca2+ disturbances as observed in BD.

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Acknowledgements

This work was supported by the Canadian Institutes of Health Research (MOP-12851, JJW, and MOP-53323, JJW and PPL), the Ontario Mental Health Foundation (JJW), and a CAMH Postdoctoral Fellowship award (SA). We gratefully acknowledge the contributions of the physicians and research staff of the Mood and Anxiety Programs of the Clarke Institute, Center for Addiction and Mental Health, and University of Toronto who referred potential patient subjects for participation in the studies from which the cell repository was established. Kin Po Siu contributed essential technical assistance in the growth and maintenance of cell lines.

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Authors and Affiliations

  1. Laboratory of Cellular and Molecular Pathophysiology, Center for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

    S Andreopoulos, M Wasserman, K Woo, P P Li & J J Warsh

  2. Departments of Biochemistry, University of Toronto, Toronto, Ontario, Canada

    S Andreopoulos

  3. Departments of Pharmacology, University of Toronto, Toronto, Ontario, Canada

    S Andreopoulos, M Wasserman, K Woo, P P Li & J J Warsh

  4. Departments of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    P P Li & J J Warsh

  5. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    J J Warsh

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  1. S Andreopoulos
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Correspondence to J J Warsh.

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Andreopoulos, S., Wasserman, M., Woo, K. et al. Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels. Pharmacogenomics J 4, 365–373 (2004). https://doi.org/10.1038/sj.tpj.6500266

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