학술논문

Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels
Document Type
Academic Journal
Source
The Pharmacogenomics Journal. Jan 01, 2004 4(6):365-373
Subject
Language
English
ISSN
1470-269X
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 (Ca) responses. As these findings suggest that chronic lithium treatment modifies receptor (ROCE) and/or store-operated Ca 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 Ca disturbances as observed in BD.