RT Journal Article
SR Electronic
T1 Effects of valproate on serotonin-induced intracellular calcium mobilization in human platelets
JF Journal of Psychiatry and Neuroscience
JO JPN
FD Canadian Medical Association
SP 17
OP 22
VO 32
IS 1
A1 Tatsuyuki Akimoto
A1 Ichiro Kusumi
A1 Katsuji Suzuki
A1 Takuya Masui
A1 Tsukasa Koyama
YR 2007
UL http://jpn.ca/content/32/1/17.abstract
AB 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.