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Published on: November 29, 2024
Effects of valproate on serotonin-induced intracellular calcium mobilization in human platelets
Tatsuyuki Akimoto1, Ichiro Kusumi, Katsuji Suzuki
1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Objective:
Valproate (VPA) is effectively used in the treatment of bipolar disorder, although the mechanism of action is unclear. In patients with bipolar disorder, 5-hydroxytryptamine (5-HT)-induced intraplatelet calcium (Ca) mobilization has been shown to be enhanced.
Methods:
We examined the effect of VPA on 5-HT-induced Ca response in the platelets of normal subjects, in the presence of a calmodulin antagonist W-7 (N-[6-aminohexyl]-5-chloro-1-naphthalenesulfonamide), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) or PKC inhibitors staurosporine and bisindolylmaleimide II.
Results:
VPA inhibited the 5-HT-induced Ca response in a concentration-dependent manner. For calmodulin pathways, W-7 enhanced the 5-HT-stimulated Ca response, which was not affected by VPA. For PKC pathways, PMA reduced the Ca response, although both PKC inhibitors had no effect. PMA, staurosporine or bisindolylmaleimide II reversed the inhibitory effect of VPA on the Ca response, while W-7 did not modify it.
Conclusion:
These findings suggest the possibility that the mechanism of action of VPA may be partly related to PKC signalling.
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